Implementación de un cultivo neuronal primario como modelo para el estudio de mecanismos de modulación sobre la vía de señalización de los fosfoinositoles
ilustraciones, fotografías, gráficas
- Autores:
-
Mantilla Esparza, Fabián Andrés
- Tipo de recurso:
- Fecha de publicación:
- 2021
- Institución:
- Universidad Nacional de Colombia
- Repositorio:
- Universidad Nacional de Colombia
- Idioma:
- spa
- OAI Identifier:
- oai:repositorio.unal.edu.co:unal/81116
- Palabra clave:
- 570 - Biología::571 - Fisiología y temas relacionados
Enzymes
Purkinje Cells
Enzimas
Células de Purkinje
Neurons
Neuronas
Litio
Célula de Purkinje
Trastorno bipolar
Embrión de pollo
Proteína Gq
Cultivo celular primario
Fosfolipasa C
Lithium
Purkinje cell
Bipolar disorder
Chick embryo
Gq protein
Primary cell culture
Phospholipase C
- Rights
- openAccess
- License
- Atribución-NoComercial-SinDerivadas 4.0 Internacional
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oai_identifier_str |
oai:repositorio.unal.edu.co:unal/81116 |
network_acronym_str |
UNACIONAL2 |
network_name_str |
Universidad Nacional de Colombia |
repository_id_str |
|
dc.title.spa.fl_str_mv |
Implementación de un cultivo neuronal primario como modelo para el estudio de mecanismos de modulación sobre la vía de señalización de los fosfoinositoles |
dc.title.translated.eng.fl_str_mv |
Implementation of a primary neuronal culture as a model for the study of modulatory mechanisms on the phosphoinositide signaling pathway |
title |
Implementación de un cultivo neuronal primario como modelo para el estudio de mecanismos de modulación sobre la vía de señalización de los fosfoinositoles |
spellingShingle |
Implementación de un cultivo neuronal primario como modelo para el estudio de mecanismos de modulación sobre la vía de señalización de los fosfoinositoles 570 - Biología::571 - Fisiología y temas relacionados Enzymes Purkinje Cells Enzimas Células de Purkinje Neurons Neuronas Litio Célula de Purkinje Trastorno bipolar Embrión de pollo Proteína Gq Cultivo celular primario Fosfolipasa C Lithium Purkinje cell Bipolar disorder Chick embryo Gq protein Primary cell culture Phospholipase C |
title_short |
Implementación de un cultivo neuronal primario como modelo para el estudio de mecanismos de modulación sobre la vía de señalización de los fosfoinositoles |
title_full |
Implementación de un cultivo neuronal primario como modelo para el estudio de mecanismos de modulación sobre la vía de señalización de los fosfoinositoles |
title_fullStr |
Implementación de un cultivo neuronal primario como modelo para el estudio de mecanismos de modulación sobre la vía de señalización de los fosfoinositoles |
title_full_unstemmed |
Implementación de un cultivo neuronal primario como modelo para el estudio de mecanismos de modulación sobre la vía de señalización de los fosfoinositoles |
title_sort |
Implementación de un cultivo neuronal primario como modelo para el estudio de mecanismos de modulación sobre la vía de señalización de los fosfoinositoles |
dc.creator.fl_str_mv |
Mantilla Esparza, Fabián Andrés |
dc.contributor.advisor.spa.fl_str_mv |
Gómez Correa, María del Pilar Nasi Lignarolo, Enrico |
dc.contributor.author.spa.fl_str_mv |
Mantilla Esparza, Fabián Andrés |
dc.contributor.researchgroup.spa.fl_str_mv |
Biofísica de la Señalización Celular |
dc.subject.ddc.spa.fl_str_mv |
570 - Biología::571 - Fisiología y temas relacionados |
topic |
570 - Biología::571 - Fisiología y temas relacionados Enzymes Purkinje Cells Enzimas Células de Purkinje Neurons Neuronas Litio Célula de Purkinje Trastorno bipolar Embrión de pollo Proteína Gq Cultivo celular primario Fosfolipasa C Lithium Purkinje cell Bipolar disorder Chick embryo Gq protein Primary cell culture Phospholipase C |
dc.subject.decs.eng.fl_str_mv |
Enzymes Purkinje Cells |
dc.subject.decs.spa.fl_str_mv |
Enzimas Células de Purkinje |
dc.subject.lemb.eng.fl_str_mv |
Neurons |
dc.subject.lemb.spa.fl_str_mv |
Neuronas |
dc.subject.proposal.spa.fl_str_mv |
Litio Célula de Purkinje Trastorno bipolar Embrión de pollo Proteína Gq Cultivo celular primario Fosfolipasa C |
dc.subject.proposal.eng.fl_str_mv |
Lithium Purkinje cell Bipolar disorder Chick embryo Gq protein Primary cell culture Phospholipase C |
description |
ilustraciones, fotografías, gráficas |
publishDate |
2021 |
dc.date.issued.none.fl_str_mv |
2021 |
dc.date.accessioned.none.fl_str_mv |
2022-03-02T20:09:50Z |
dc.date.available.none.fl_str_mv |
2022-03-02T20:09:50Z |
dc.type.spa.fl_str_mv |
Trabajo de grado - Maestría |
dc.type.driver.spa.fl_str_mv |
info:eu-repo/semantics/masterThesis |
dc.type.version.spa.fl_str_mv |
info:eu-repo/semantics/acceptedVersion |
dc.type.content.spa.fl_str_mv |
Text |
dc.type.redcol.spa.fl_str_mv |
http://purl.org/redcol/resource_type/TM |
status_str |
acceptedVersion |
dc.identifier.uri.none.fl_str_mv |
https://repositorio.unal.edu.co/handle/unal/81116 |
dc.identifier.instname.spa.fl_str_mv |
Universidad Nacional de Colombia |
dc.identifier.reponame.spa.fl_str_mv |
Repositorio Institucional Universidad Nacional de Colombia |
dc.identifier.repourl.spa.fl_str_mv |
https://repositorio.unal.edu.co/ |
url |
https://repositorio.unal.edu.co/handle/unal/81116 https://repositorio.unal.edu.co/ |
identifier_str_mv |
Universidad Nacional de Colombia Repositorio Institucional Universidad Nacional de Colombia |
dc.language.iso.spa.fl_str_mv |
spa |
language |
spa |
dc.relation.references.spa.fl_str_mv |
Ache, B. W., & Young, J. M. (2005). Olfaction: Diverse Species, Conserved Principles. Neuron, 48(3), 417-430. https://doi.org/10.1016/j.neuron.2005.10.022 Aiba, A., Kano, M., Chen, C., Stanton, M. E., Fox, G. D., Herrup, K., Zwingman, T. A., & Tonegawa, S. (1994). Deficient cerebellar long-term depression and impaired motor learning in mGluR1 mutant mice. Cell, 79(2), 377-388. Akar, S., & Sur, E. (2010). The development of chicken cerebellar cortex and the determination of AgNOR activity of the Purkinje cell nuclei. Belgian Journal of Zoology, 140. Allison, J. H., & Stewart, M. A. (1971). Reduced brain inositol in lithium-treated rats. Nature: New Biology, 233(43), 267-268. https://doi.org/10.1038/newbio233267a0 Aloulou, A., Rahier, R., Arhab, Y., Noiriel, A., & Abousalham, A. (2018). Phospholipases: An Overview. Methods in Molecular Biology (Clifton, N.J.), 1835, 69-105. https://doi.org/10.1007/978-1-4939-8672-9_3 Angueyra, J. M., Pulido, C., Malagón, G., Nasi, E., & Gomez, M. del P. (2012). Melanopsin-Expressing Amphioxus Photoreceptors Transduce Light via a Phospholipase C Signaling Cascade. PLoS ONE, 7(1), e29813. https://doi.org/10.1371/journal.pone.0029813 Ardeshiri, A., Kelley, M. H., Korner, I. P., Hurn, P. D., & Herson, P. S. (2006). Mechanism of progesterone neuroprotection of rat cerebellar Purkinje cells following oxygen–glucose deprivation. European Journal of Neuroscience, 24(9), 2567-2574. https://doi.org/10.1111/j.1460-9568.2006.05142.x Arora, M. (2013). Cell Culture Media: A Review. MATER METHODS, 3(175), 24. https://doi.org///dx.doi.org/10.13070/mm.en.3.175 Audinat, E., Knöpfel, T., & Gähwiler, B. H. (1990). Responses to excitatory amino acids of Purkinje cells’ and neurones of the deep nuclei in cerebellar slice cultures. The Journal of Physiology, 430, 297-313. https://doi.org/10.1113/jphysiol.1990.sp018292 Avissar, S., Murphy, D. L., & Schreiber, G. (1991). Magnesium reversal of lithium inhibition of beta-adrenergic and muscarinic receptor coupling to G proteins. Biochemical Pharmacology, 41(2), 171-175. https://doi.org/10.1016/0006-2952(91)90473-i Avissar, S., & Schreiber, G. (1992). The involvement of guanine nucleotide binding proteins in the pathogenesis and treatment of affective disorders. Biological Psychiatry, 31(5), 435-459. https://doi.org/10.1016/0006-3223(92)90257-z Avissar, S., Schreiber, G., Danon, A., & Belmaker, R. H. (1988). Lithium inhibits adrenergic and cholinergic increases in GTP binding in rat cortex. Nature, 331(6155), 440-442. https://doi.org/10.1038/331440a0 Báez-Becerra, C., Filipello, F., Sandoval-Hernández, A., Arboleda, H., & Arboleda, G. (2018). Liver X Receptor Agonist GW3965 Regulates Synaptic Function upon Amyloid Beta Exposure in Hippocampal Neurons. Neurotoxicity Research, 33(3), 569-579. https://doi.org/10.1007/s12640-017-9845-3 Baptista, C. A., Hatten, M. E., Blazeski, R., & Mason, C. A. (1994). Cell-cell interactions influence survival and differentiation of purified Purkinje cells in vitro. Neuron, 12(2), 243-260. https://doi.org/10.1016/0896-6273(94)90268-2 Bastianelli, E., & Pochet, R. (1993). Transient expression of calretinin during development of chick cerebellum. Comparison with calbindin-D28k. Neuroscience Research, 17(1), 53-61. https://doi.org/10.1016/0168-0102(93)90029-p Batchelor, A. M., Madge, D. J., & Garthwaite, J. (1994). Synaptic activation of metabotropic glutamate receptors in the parallel fibre-Purkinje cell pathway in rat cerebellar slices. Neuroscience, 63(4), 911-915. https://doi.org/10.1016/0306-4522(94)90558-4 Bearden, C. E., Thompson, P. M., Dalwani, M., Hayashi, K. M., Lee, A. D., Nicoletti, M., Trakhtenbroit, M., Glahn, D. C., Brambilla, P., Sassi, R. B., Mallinger, A. G., Frank, E., Kupfer, D. J., & Soares, J. C. (2007). Greater cortical gray matter density in lithium-treated patients with bipolar disorder. Biological Psychiatry, 62(1), 7-16. https://doi.org/10.1016/j.biopsych.2006.10.027 Berk, M., Dodd, S., Kauer-Sant’anna, M., Malhi, G. S., Bourin, M., Kapczinski, F., & Norman, T. (2007). Dopamine dysregulation syndrome: Implications for a dopamine hypothesis of bipolar disorder. Acta Psychiatrica Scandinavica. Supplementum, 434, 41-49. https://doi.org/10.1111/j.1600-0447.2007.01058.x Berridge, M. J., Downes, C. P., & Hanley, M. R. (1989). Neural and developmental actions of lithium: A unifying hypothesis. Cell, 59(3), 411-419. https://doi.org/10.1016/0092-8674(89)90026-3 Berridge, M. J., & Irvine, R. F. (1984). Inositol trisphosphate, a novel second messenger in cellular signal transduction. Nature, 312(5992), 315-321. https://doi.org/10.1038/312315a0 Bertossi, M., Roncali, L., Mancini, L., Ribatti, D., & Nico, B. (1986). Process of differentiation of cerebellar Purkinje neurons in the chick embryo. Anatomy and Embryology, 175(1), 25-34. https://doi.org/10.1007/BF00315453 Beurel, E., & Jope, R. S. (2006). The paradoxical pro- and anti-apoptotic actions of GSK3 in the intrinsic and extrinsic apoptosis signaling pathways. Progress in Neurobiology, 79(4), 173-189. https://doi.org/10.1016/j.pneurobio.2006.07.006 Bezprozvanny, L., Watras, J., & Ehrlich, B. E. (1991). Bell-shaped calcium-response curves of lns(l,4,5)P 3—And calcium-gated channels from endoplasmic reticulum of cerebellum. Nature, 351(6329), 751-754. https://doi.org/10.1038/351751a0 Brorson, J. R., Bleakman, D., Gibbons, S. J., & Miller, R. J. (1991). The properties of intracellular calcium stores in cultured rat cerebellar neurons. The Journal of Neuroscience: The Official Journal of the Society for Neuroscience, 11(12), 4024-4043. Butler-Munro, C., Coddington, E. J., Shirley, C. H., & Heyward, P. M. (2010). Lithium modulates cortical excitability in vitro. Brain Research, 1352, 50-60. https://doi.org/10.1016/j.brainres.2010.07.021 Caraux, A., Kim, N., Bell, S. E., Zompi, S., Ranson, T., Lesjean-Pottier, S., Garcia-Ojeda, M. E., Turner, M., & Colucci, F. (2006). Phospholipase C-γ2 is essential for NK cell cytotoxicity and innate immunity to malignant and virally infected cells. Blood, 107(3), 994-1002. https://doi.org/10.1182/blood-2005-06-2428 Carli, M., Anand-Srivastava, M. B., Molina-Holgado, E., Dewar, K. M., & Reader, T. A. (1994). Effects of chronic lithium treatments on central dopaminergic receptor systems: G proteins as possible targets. Neurochemistry International, 24(1), 13-22. https://doi.org/10.1016/0197-0186(94)90124-4 Casebolt, T. L., & Jope, R. S. (1987). Chronic lithium treatment reduces norepinephrine-stimulated inositol phospholipid hydrolysis in rat cortex. European Journal of Pharmacology, 140(2), 245-246. https://doi.org/10.1016/0014-2999(87)90813-2 Clapham, D. E. (2007). Calcium Signaling. Cell, 131(6), 1047-1058. https://doi.org/10.1016/j.cell.2007.11.028 Cohen-Cory, S., Dreyfus, C. F., & Black, I. B. (1991). NGF and excitatory neurotransmitters regulate survival and morphogenesis of cultured cerebellar Purkinje cells. The Journal of Neuroscience: The Official Journal of the Society for Neuroscience, 11(2), 462-471. Conquet, F., Bashir, Z. I., Davies, C. H., Daniel, H., Ferraguti, F., Bordi, F., Franz-Bacon, K., Reggiani, A., Matarese, V., & Condé, F. (1994). Motor deficit and impairment of synaptic plasticity in mice lacking mGluR1. Nature, 372(6503), 237-243. https://doi.org/10.1038/372237a0 Consalez, G. G., Goldowitz, D., Casoni, F., & Hawkes, R. (2020). Origins, Development, and Compartmentation of the Granule Cells of the Cerebellum. Frontiers in Neural Circuits, 14, 611841. https://doi.org/10.3389/fncir.2020.611841 Davies, J. A. (2007). Metabotropic Glutamate Receptor Agents. En S. J. Enna & D. B. Bylund (Eds.), XPharm: The Comprehensive Pharmacology Reference (pp. 1-2). Elsevier. https://doi.org/10.1016/B978-008055232-3.60987-0 Dixon, J. F., & Hokin, L. E. (1998). Lithium acutely inhibits and chronically up-regulates and stabilizes glutamate uptake by presynaptic nerve endings in mouse cerebral cortex. Proceedings of the National Academy of Sciences of the United States of America, 95(14), 8363-8368. https://doi.org/10.1073/pnas.95.14.8363 Durán Ferro, S. (2016). Inmunodetección de las proteínas de la cascada de fosfoinositoles en células HEK293 y evaluación de los efectos del litio sobre corrientes de membrana activadas por esta vía [Tesis de Maestría, Universidad Nacional de Colombia - Sede Bogotá]. https://repositorio.unal.edu.co/handle/unal/59178 Dzubay, J. A., & Otis, T. S. (2002). Climbing fiber activation of metabotropic glutamate receptors on cerebellar purkinje neurons. Neuron, 36(6), 1159-1167. https://doi.org/10.1016/s0896-6273(02)01052-8 Empson, R. M., & Knöpfel, T. (2012). Functional integration of calcium regulatory mechanisms at Purkinje neuron synapses. Cerebellum (London, England), 11(3), 640-650. https://doi.org/10.1007/s12311-010-0185-6 Faber, E. S. L., Sedlak, P., Vidovic, M., & Sah, P. (2006). Synaptic activation of transient receptor potential channels by metabotropic glutamate receptors in the lateral amygdala. Neuroscience, 137(3), 781-794. https://doi.org/10.1016/j.neuroscience.2005.09.027 Fain, G. L., Hardie, R., & Laughlin, S. B. (2010). Phototransduction and the Evolution of Photoreceptors. Current Biology, 20(3), R114-R124. https://doi.org/10.1016/j.cub.2009.12.006 Fleming, J. T., He, W., Hao, C., Ketova, T., Pan, F. C., Wright, C. C. V., Litingtung, Y., & Chiang, C. (2013). The Purkinje Neuron Acts as a Central Regulator of Spatially and Functionally Distinct Cerebellar Precursors. Developmental Cell, 27(3), 278-292. https://doi.org/10.1016/j.devcel.2013.10.008 Foelix, R. F., & Oppenheim, R. (1974). The development of synapses in the cerebellar cortex of the chick embryo. Journal of Neurocytology, 3(3), 277-294. https://doi.org/10.1007/BF01097914 Forsythe, I. D., Lambert, D. G., Nahorski, S. R., & Lindsdell, P. (1992). Elevation of cytosolic calcium by cholinoceptor agonists in SH-SY5Y human neuroblastoma cells: Estimation of the contribution of voltage-dependent currents. British Journal of Pharmacology, 107(1), 207-214. https://doi.org/10.1111/j.1476-5381.1992.tb14488.x Fountoulakis, K. N., Vieta, E., Sanchez-Moreno, J., Kaprinis, S. G., Goikolea, J. M., & Kaprinis, G. S. (2005). Treatment guidelines for bipolar disorder: A critical review. Journal of Affective Disorders, 86(1), 1-10. https://doi.org/10.1016/j.jad.2005.01.004 Fujishima, K., Horie, R., Mochizuki, A., & Kengaku, M. (2012). Principles of branch dynamics governing shape characteristics of cerebellar Purkinje cell dendrites. Development, 139(18), 3442-3455. https://doi.org/10.1242/dev.081315 Fujishima, K., Kawabata Galbraith, K., & Kengaku, M. (2018). Dendritic Self-Avoidance and Morphological Development of Cerebellar Purkinje Cells. Cerebellum (London, England), 17(6), 701-708. https://doi.org/10.1007/s12311-018-0984-8 Fukami, K., Inanobe, S., Kanemaru, K., & Nakamura, Y. (2010). Phospholipase C is a key enzyme regulating intracellular calcium and modulating the phosphoinositide balance. Progress in Lipid Research, 49(4), 429-437. https://doi.org/10.1016/j.plipres.2010.06.001 Fukumoto, T., Morinobu, S., Okamoto, Y., Kagaya, A., & Yamawaki, S. (2001). Chronic lithium treatment increases the expression of brain-derived neurotrophic factor in the rat brain. Psychopharmacology, 158(1), 100-106. https://doi.org/10.1007/s002130100871 Furuya, S., Makino, A., & Hirabayashi, Y. (1998). An improved method for culturing cerebellar Purkinje cells with differentiated dendrites under a mixed monolayer setting. Brain Research. Brain Research Protocols, 3(2), 192-198. https://doi.org/10.1016/s1385-299x(98)00040-3 Geddes, J. R., & Miklowitz, D. J. (2013). Treatment of bipolar disorder. The Lancet, 381(9878), 1672-1682. https://doi.org/10.1016/S0140-6736(13)60857-0 Giussani, D. A., Salinas, C. E., Villena, M., & Blanco, C. E. (2007). The role of oxygen in prenatal growth: Studies in the chick embryo. The Journal of Physiology, 585(Pt 3), 911-917. https://doi.org/10.1113/jphysiol.2007.141572 Godfrey, P. P., McClue, S. J., White, A. M., Wood, A. J., & Grahame-Smith, D. G. (1989). Subacute and chronic in vivo lithium treatment inhibits agonist- and sodium fluoride-stimulated inositol phosphate production in rat cortex. Journal of Neurochemistry, 52(2), 498-506. https://doi.org/10.1111/j.1471-4159.1989.tb09148.x Gomez, L. C., Kawaguchi, S.-Y., Collin, T., Jalil, A., Gomez, M. D. P., Nasi, E., Marty, A., & Llano, I. (2020). Influence of spatially segregated IP3-producing pathways on spike generation and transmitter release in Purkinje cell axons. Proceedings of the National Academy of Sciences of the United States of America, 117(20), 11097-11108. https://doi.org/10.1073/pnas.2000148117 Grande, I., Berk, M., Birmaher, B., & Vieta, E. (2016). Bipolar disorder. The Lancet, 387(10027), 1561-1572. https://doi.org/10.1016/S0140-6736(15)00241-X Grimes, C. A., & Jope, R. S. (2001). The multifaceted roles of glycogen synthase kinase 3beta in cellular signaling. Progress in Neurobiology, 65(4), 391-426. https://doi.org/10.1016/s0301-0082(01)00011-9 Grunze, H., Vieta, E., Goodwin, G. M., Bowden, C., Licht, R. W., Azorin, J.-M., Yatham, L., Mosolov, S., Möller, H.-J., Kasper, S., & Members of the WFSBP Task Force on Bipolar Affective Disorders Working on this topic. (2018). The World Federation of Societies of Biological Psychiatry (WFSBP) Guidelines for the Biological Treatment of Bipolar Disorders: Acute and long-term treatment of mixed states in bipolar disorder. The World Journal of Biological Psychiatry: The Official Journal of the World Federation of Societies of Biological Psychiatry, 19(1), 2-58. https://doi.org/10.1080/15622975.2017.1384850 Hallcher, L. M., & Sherman, W. R. (1980). The effects of lithium ion and other agents on the activity of myo-inositol-1-phosphatase from bovine brain. The Journal of Biological Chemistry, 255(22), 10896-10901. Hamburger, V., & Hamilton, H. L. (1951). A series of normal stages in the development of the chick embryo. Journal of Morphology, 88(1), 49-92. https://doi.org/10.1002/jmor.1050880104 Harrison, P. J., Geddes, J. R., & Tunbridge, E. M. (2018). The Emerging Neurobiology of Bipolar Disorder. Trends in Neurosciences, 41(1), 18-30. https://doi.org/10.1016/j.tins.2017.10.006 Hartmann, J., & Konnerth, A. (2009). Mechanisms of metabotropic glutamate receptor-mediated synaptic signalling in cerebellar Purkinje cells. Acta Physiologica, 195(1), 79-90. https://doi.org/10.1111/j.1748-1716.2008.01923.x Heintz, T. G., Eva, R., & Fawcett, J. W. (2016). Regional Regulation of Purkinje Cell Dendritic Spines by Integrins and Eph/Ephrins. PLOS ONE, 11(8), e0158558. https://doi.org/10.1371/journal.pone.0158558 Hibar, D. P., Westlye, L. T., Doan, N. T., Jahanshad, N., Cheung, J. W., Ching, C. R. K., Versace, A., Bilderbeck, A. C., Uhlmann, A., Mwangi, B., Krämer, B., Overs, B., Hartberg, C. B., Abé, C., Dima, D., Grotegerd, D., Sprooten, E., Bøen, E., Jimenez, E., … Andreassen, O. A. (2018). Cortical abnormalities in bipolar disorder: An MRI analysis of 6503 individuals from the ENIGMA Bipolar Disorder Working Group. Molecular Psychiatry, 23(4), 932-942. https://doi.org/10.1038/mp.2017.73 Hibar, D. P., Westlye, L. T., van Erp, T. G. M., Rasmussen, J., Leonardo, C. D., Faskowitz, J., Haukvik, U. K., Hartberg, C. B., Doan, N. T., Agartz, I., Dale, A. M., Gruber, O., Krämer, B., Trost, S., Liberg, B., Abé, C., Ekman, C. J., Ingvar, M., Landén, M., … Andreassen, O. A. (2016). Subcortical volumetric abnormalities in bipolar disorder. Molecular Psychiatry, 21(12), 1710-1716. https://doi.org/10.1038/mp.2015.227 Hilgemann, D. W. (2007). On the physiological roles of PIP2 at cardiac Na+–Ca2+ exchangers and KATP channels: A long journey from membrane biophysics into cell biology. The Journal of Physiology, 582(Pt 3), 903-909. https://doi.org/10.1113/jphysiol.2007.132746 Hinoi, E., Ogita, K., Takeuchi, Y., Ohashi, H., Maruyama, T., & Yoneda, Y. (2001). Characterization with [3H]quisqualate of group I metabotropic glutamate receptor subtype in rat central and peripheral excitable tissues. Neurochemistry International, 38(3), 277-285. https://doi.org/10.1016/s0197-0186(00)00075-9 Hirano, T. (2018). Regulation and Interaction of Multiple Types of Synaptic Plasticity in a Purkinje Neuron and Their Contribution to Motor Learning. Cerebellum (London, England), 17(6), 756-765. https://doi.org/10.1007/s12311-018-0963-0 Hirano, T., & Hagiwara, S. (1989). Kinetics and distribution of voltage-gated Ca, Na and K channels on the somata of rat cerebellar Purkinje cells. Pflugers Archiv: European Journal of Physiology, 413(5), 463-469. https://doi.org/10.1007/BF00594174 Hockberger, P. E., Tseng, H. Y., & Connor, J. A. (1989a). Development of rat cerebellar Purkinje cells: Electrophysiological properties following acute isolation and in long-term culture. The Journal of Neuroscience: The Official Journal of the Society for Neuroscience, 9(7), 2258-2271. Hockberger, P. E., Tseng, H. Y., & Connor, J. A. (1989b). Development of rat cerebellar Purkinje cells: Electrophysiological properties following acute isolation and in long-term culture. The Journal of Neuroscience: The Official Journal of the Society for Neuroscience, 9(7), 2258-2271. Huang, C.-L. (2007). Complex roles of PIP2 in the regulation of ion channels and transporters. American Journal of Physiology. Renal Physiology, 293(6), F1761-1765. https://doi.org/10.1152/ajprenal.00400.2007 Hurowitz, E. H., Melnyk, J. M., Chen, Y.-J., Kouros-Mehr, H., Simon, M. I., & Shizuya, H. (2000). Genomic Characterization of the Human Heterotrimeric G Protein α, β, and γ Subunit Genes. DNA Research, 7(2), 111-120. https://doi.org/10.1093/dnares/7.2.111 Hussain, S., Gardner, C. R., Bagust, J., & Walker, R. J. (1991). Receptor sub-types involved in responses of Purkinje cell to exogenous excitatory amino acids and local electrical stimulation in cerebellar slices in the rat. Neuropharmacology, 30(10), 1029-1037. https://doi.org/10.1016/0028-3908(91)90130-4 Ichise, T., Kano, M., Hashimoto, K., Yanagihara, D., Nakao, K., Shigemoto, R., Katsuki, M., & Aiba, A. (2000). MGluR1 in Cerebellar Purkinje Cells Essential for Long-Term Depression, Synapse Elimination, and Motor Coordination. Science, 288(5472), 1832-1835. https://doi.org/10.1126/science.288.5472.1832 Ito, M. (1987). Signal processing in cerebellar Purkinje cells. Physiologia Bohemoslovaca, 36(3), 203-216. Ito, M. (2001). Cerebellar Long-Term Depression: Characterization, Signal Transduction, and Functional Roles. Physiological Reviews, 81(3), 1143-1195. https://doi.org/10.1152/physrev.2001.81.3.1143 Ito, M. (2002). Historical review of the significance of the cerebellum and the role of Purkinje cells in motor learning. Annals of the New York Academy of Sciences, 978, 273-288. https://doi.org/10.1111/j.1749-6632.2002.tb07574.x Ito, M., & Karachot, L. (1990). Messengers mediating long-term desensitization in cerebellar Purkinje cells. Neuroreport, 1(2), 129-132. https://doi.org/10.1097/00001756-199010000-00012 Itsuki, K., Imai, Y., Hase, H., Okamura, Y., Inoue, R., & Mori, M. X. (2014). PLC-mediated PI(4,5)P2 hydrolysis regulates activation and inactivation of TRPC6/7 channels. The Journal of General Physiology, 143(2), 183-201. https://doi.org/10.1085/jgp.201311033 Jeffrey, P. L., Meaney, J., Tolhurst, O., & Weinberger, R. P. (1996). Epigenetic factors controlling the development of avian Purkinje neurons. Journal of Neuroscience Methods, 67(2), 163-175. Jope, R. S. (1999). Anti-bipolar therapy: Mechanism of action of lithium. Molecular Psychiatry, 4(2), 117-128. https://doi.org/10.1038/sj.mp.4000494 Jope, R. S. (2003). Lithium and GSK-3: One inhibitor, two inhibitory actions, multiple outcomes. Trends in Pharmacological Sciences, 24(9), 441-443. https://doi.org/10.1016/S0165-6147(03)00206-2 Jope, R. S., & Williams, M. B. (1994). Lithium and brain signal transduction systems. Biochemical Pharmacology, 47(3), 429-441. https://doi.org/10.1016/0006-2952(94)90172-4 Kadamur, G., & Ross, E. M. (2013). Mammalian Phospholipase C. Annual Review of Physiology, 75(1), 127-154. https://doi.org/10.1146/annurev-physiol-030212-183750 Kandel, E. R., Schwartz, J. H., Jessell, T. M., Siegelbaum, S. A., & Hudspeth, A. J. (Eds.). (2012). Principles of Neural Science. Kano, M., & Kato, M. (1987a). Quisqualate receptors are specifically involved in cerebellar synaptic plasticity. Nature, 325(6101), 276-279. https://doi.org/10.1038/325276a0 Kano, M., & Kato, M. (1987b). Quisqualate receptors are specifically involved in cerebellar synaptic plasticity. Nature, 325(6101), 276-279. https://doi.org/10.1038/325276a0 Kapfhammer, J. P. (2004). Cellular and molecular control of dendritic growth and development of cerebellar Purkinje cells. Progress in Histochemistry and Cytochemistry, 39(3), 131-182. https://doi.org/10.1016/j.proghi.2004.07.002 Kendall, D. A., & Nahorski, S. R. (1987). Acute and chronic lithium treatments influence agonist and depolarization-stimulated inositol phospholipid hydrolysis in rat cerebral cortex. The Journal of Pharmacology and Experimental Therapeutics, 241(3), 1023-1027. Kim, D., Jun, K. S., Lee, S. B., Kang, N.-G., Min, D. S., Kim, Y.-H., Ryu, S. H., Suh, P.-G., & Shin, H.-S. (1997). Phospholipase C isozymes selectively couple to specific neurotransmitter receptors. Nature, 389(6648), 290-293. https://doi.org/10.1038/38508 Kitamura, K., & Kano, M. (2013). Dendritic calcium signaling in cerebellar Purkinje cell. Neural Networks: The Official Journal of the International Neural Network Society, 47, 11-17. https://doi.org/10.1016/j.neunet.2012.08.001 Knöpfel, T., Anchisi, D., Alojado, M. E., Tempia, F., & Strata, P. (2000). Elevation of intradendritic sodium concentration mediated by synaptic activation of metabotropic glutamate receptors in cerebellar Purkinje cells. The European Journal of Neuroscience, 12(6), 2199-2204. https://doi.org/10.1046/j.1460-9568.2000.00122.x Knöpfel, T., & Grandes, P. (2002). Metabotropic glutamate receptors in the cerebellum with a focus on their function in Purkinje cells. Cerebellum (London, England), 1(1), 19-26. https://doi.org/10.1007/BF02941886 Lambert, D. G., & Nahorski, S. R. (1990). Muscarinic-receptor-mediated changes in intracellular Ca2+ and inositol 1,4,5-trisphosphate mass in a human neuroblastoma cell line, SH-SY5Y. The Biochemical Journal, 265(2), 555-562. https://doi.org/10.1042/bj2650555 Landinez Macias, M. P. (2016). Evaluación fisiológica de los efectos del litio sobre la movilización de calcio intracelular en la línea celular HEK 293 [Tesis de Maestría, Universidad Nacional de Colombia - Sede Bogotá]. https://repositorio.unal.edu.co/handle/unal/56608 Lee, C. H., Park, D., Wu, D., Rhee, S. G., & Simon, M. I. (1992). Members of the Gq alpha subunit gene family activate phospholipase C beta isozymes. Journal of Biological Chemistry, 267(23), 16044-16047. Lindemann, B. (2001). Receptors and transduction in taste. Nature, 413(6852), 219-225. https://doi.org/10.1038/35093032 Linden, D. J., Dickinson, M. H., Smeyne, M., & Connor, J. A. (1991). A long-term depression of AMPA currents in cultured cerebellar Purkinje neurons. Neuron, 7(1), 81-89. https://doi.org/10.1016/0896-6273(91)90076-c Linden, D. J., Smeyne, M., & Connor, J. A. (1994). Trans-ACPD, a metabotropic receptor agonist, produces calcium mobilization and an inward current in cultured cerebellar Purkinje neurons. Journal of Neurophysiology, 71(5), 1992-1998. https://doi.org/10.1152/jn.1994.71.5.1992 Livingstone, C., & Rampes, H. (2006). Lithium: A review of its metabolic adverse effects. Journal of Psychopharmacology, 20(3), 347-355. https://doi.org/10.1177/0269881105057515 Llano, I., Dreessen, J., Kano, M., & Konnerth, A. (1991). Intradendritic release of calcium induced by glutamate in cerebellar Purkinje cells. Neuron, 7(4), 577-583. https://doi.org/10.1016/0896-6273(91)90370-f Llinás, R., & Sugimori, M. (1980). Electrophysiological properties of in vitro Purkinje cell somata in mammalian cerebellar slices. The Journal of Physiology, 305, 171-195. Lydiard, R. B., & Gelenberg, A. J. (1982). Hazards and adverse effects of lithium. Annual Review of Medicine, 33, 327-344. https://doi.org/10.1146/annurev.me.33.020182.001551 Malhi, G. S., Adams, D., & Berk, M. (2009). Is lithium in a class of its own? A brief profile of its clinical use. The Australian and New Zealand Journal of Psychiatry, 43(12), 1096-1104. https://doi.org/10.3109/00048670903279937 Malhi, G. S., & Tanious, M. (2011). Optimal frequency of lithium administration in the treatment of bipolar disorder: Clinical and dosing considerations. CNS Drugs, 25(4), 289-298. https://doi.org/10.2165/11586970-000000000-00000 Malhi, G. S., Tanious, M., Das, P., Coulston, C. M., & Berk, M. (2013). Potential Mechanisms of Action of Lithium in Bipolar Disorder. CNS Drugs, 27(2), 135-153. https://doi.org/10.1007/s40263-013-0039-0 Marcaggi, P. (2015). Cerebellar endocannabinoids: Retrograde signaling from purkinje cells. Cerebellum (London, England), 14(3), 341-353. https://doi.org/10.1007/s12311-014-0629-5 Masana, M. I., Bitran, J. A., Hsiao, J. K., & Potter, W. Z. (1992). In vivo evidence that lithium inactivates Gi modulation of adenylate cyclase in brain. Journal of Neurochemistry, 59(1), 200-205. https://doi.org/10.1111/j.1471-4159.1992.tb08891.x Mathews, R., Li, P. P., Young, L. T., Kish, S. J., & Warsh, J. J. (1997). Increased Gαq/11 immunoreactivity in postmortem occipital cortex from patients with bipolar affective disorder. Biological Psychiatry, 41(6), 649-656. https://doi.org/10.1016/S0006-3223(96)00113-8 Mayer, M. L., Crunelli, V., & Kemp, J. A. (1984). Lithium ions increase action potential duration of mammalian neurons. Brain Research, 293(1), 173-177. https://doi.org/10.1016/0006-8993(84)91466-5 McKay, B. E., & Turner, R. W. (2005). Physiological and morphological development of the rat cerebellar Purkinje cell. The Journal of Physiology, 567(Pt 3), 829-850. https://doi.org/10.1113/jphysiol.2005.089383 McKnight, R. F., Adida, M., Budge, K., Stockton, S., Goodwin, G. M., & Geddes, J. R. (2012). Lithium toxicity profile: A systematic review and meta-analysis. The Lancet, 379(9817), 721-728. https://doi.org/10.1016/S0140-6736(11)61516-X Meaney, J. A., Balcar, V. J., Rothstein, J. D., & Jeffrey, P. L. (1998). Glutamate transport in cultures from developing avian cerebellum: Presence of GLT-1 immunoreactivity in Purkinje neurons. Journal of Neuroscience Research, 54(5), 595-603. https://doi.org/10.1002/(SICI)1097-4547(19981201)54:5<595::AID-JNR4>3.0.CO;2-Q Mei, L., Yamamura, H. I., & Roeske, W. R. (1988). Muscarinic receptor-mediated hydrolysis of phosphatidylinositols in human neuroblastoma (SH-SY5Y) cells is sensitive to pertussis toxin. Brain Research, 447(2), 360-363. https://doi.org/10.1016/0006-8993(88)91140-7 Michael, N., Erfurth, A., Ohrmann, P., Gössling, M., Arolt, V., Heindel, W., & Pfleiderer, B. (2003). Acute mania is accompanied by elevated glutamate/glutamine levels within the left dorsolateral prefrontal cortex. Psychopharmacology, 168(3), 344-346. https://doi.org/10.1007/s00213-003-1440-z Milligan, G., & Kostenis, E. (2006). Heterotrimeric G-proteins: A short history. British Journal of Pharmacology, 147(S1), S46-S55. https://doi.org/10.1038/sj.bjp.0706405 Mizuno, N., & Itoh, H. (2009). Functions and regulatory mechanisms of Gq-signaling pathways. Neuro-Signals, 17(1), 42-54. https://doi.org/10.1159/000186689 Monsivais, P., Clark, B. A., Roth, A., & Häusser, M. (2005). Determinants of Action Potential Propagation in Cerebellar Purkinje Cell Axons. The Journal of Neuroscience, 25(2), 464-472. https://doi.org/10.1523/JNEUROSCI.3871-04.2005 Müller-Oerlinghausen, B., Berghöfer, A., & Bauer, M. (2002). Bipolar disorder. Lancet (London, England), 359(9302), 241-247. https://doi.org/10.1016/S0140-6736(02)07450-0 Netzeband, J. G., Parsons, K. L., Sweeney, D. D., & Gruol, D. L. (1997). Metabotropic glutamate receptor agonists alter neuronal excitability and Ca2+ levels via the phospholipase C transduction pathway in cultured Purkinje neurons. Journal of Neurophysiology, 78(1), 63-75. https://doi.org/10.1152/jn.1997.78.1.63 Nolen, W. A., Licht, R. W., Young, A. H., Malhi, G. S., Tohen, M., Vieta, E., Kupka, R. W., Zarate, C., Nielsen, R. E., Baldessarini, R. J., & Severus, E. (2019). What is the optimal serum level for lithium in the maintenance treatment of bipolar disorder? A systematic review and recommendations from the ISBD/IGSLI Task Force on treatment with lithium. Bipolar Disorders, 21(5), 394-409. https://doi.org/10.1111/bdi.12805 Nonaka, S., Hough, C. J., & Chuang, D. M. (1998). Chronic lithium treatment robustly protects neurons in the central nervous system against excitotoxicity by inhibiting N-methyl-D-aspartate receptor-mediated calcium influx. Proceedings of the National Academy of Sciences of the United States of America, 95(5), 2642-2647. https://doi.org/10.1073/pnas.95.5.2642 Nunes, P., & Demaurex, N. (2010). The role of calcium signaling in phagocytosis. Journal of Leukocyte Biology, 88(1), 57-68. https://doi.org/10.1189/jlb.0110028 Oldham, W. M., & Hamm, H. E. (2008). Heterotrimeric G protein activation by G-protein-coupled receptors. Nature Reviews. Molecular Cell Biology, 9(1), 60-71. https://doi.org/10.1038/nrm2299 Partridge, L. D., & Thomas, R. C. (1974). Effect of intracellular lithium on snail neurones. Nature, 249(457), 578-580. https://doi.org/10.1038/249578a0 Peinado, G., Osorno, T., Gomez, M. del P., & Nasi, E. (2015). Calcium activates the light-dependent conductance in melanopsin-expressing photoreceptors of amphioxus. Proceedings of the National Academy of Sciences, 112(25), 7845-7850. https://doi.org/10.1073/pnas.1420265112 Perkel, D. J., Hestrin, S., Sah, P., & Nicoll, R. A. (1990). Excitatory synaptic currents in Purkinje cells. Proceedings. Biological Sciences, 241(1301), 116-121. https://doi.org/10.1098/rspb.1990.0074 Phillips, M. L., & Kupfer, D. J. (2013). Bipolar disorder diagnosis: Challenges and future directions. The Lancet, 381(9878), 1663-1671. https://doi.org/10.1016/S0140-6736(13)60989-7 Piochon, C., Irinopoulou, T., Brusciano, D., Bailly, Y., Mariani, J., & Levenes, C. (2007). NMDA receptor contribution to the climbing fiber response in the adult mouse Purkinje cell. The Journal of Neuroscience: The Official Journal of the Society for Neuroscience, 27(40), 10797-10809. https://doi.org/10.1523/JNEUROSCI.2422-07.2007 Ploeger, E. J. (1974). The effects of lithium on excitable cell membranes. On the mechanism of inhibition of the sodium pump of non-myelinated nerve fibres of the rat. European Journal of Pharmacology, 25(3), 316-321. https://doi.org/10.1016/0014-2999(74)90261-1 Pompili, M., Gonda, X., Serafini, G., Innamorati, M., Sher, L., Amore, M., Rihmer, Z., & Girardi, P. (2013). Epidemiology of suicide in bipolar disorders: A systematic review of the literature. Bipolar Disorders, 15(5), 457-490. https://doi.org/10.1111/bdi.12087 Ransdell, J. L., & Nerbonne, J. M. (2018). Voltage-gated sodium currents in cerebellar Purkinje neurons: Functional and molecular diversity. Cellular and Molecular Life Sciences: CMLS, 75(19), 3495-3505. https://doi.org/10.1007/s00018-018-2868-y Renshaw, P. F., & Wicklund, S. (1988). In vivo measurement of lithium in humans by nuclear magnetic resonance spectroscopy. Biological Psychiatry, 23(5), 465-475. https://doi.org/10.1016/0006-3223(88)90018-2 Reuveny, E., & Narahashi, T. (1993). Two types of high voltage-activated calcium channels in SH-SY5Y human neuroblastoma cells. Brain Research, 603(1), 64-73. https://doi.org/10.1016/0006-8993(93)91300-h Rhee, S. G. (2001). Regulation of phosphoinositide-specific phospholipase C. Annual Review of Biochemistry, 70, 281-312. https://doi.org/10.1146/annurev.biochem.70.1.281 Rossi, F., Buffo, A., & Strata, P. (2001). Regulation of intrinsic regenerative properties and axonal plasticity in cerebellar Purkinje cells. Restorative Neurology and Neuroscience, 19(1-2), 85-94. Roth, B. L. (2019). Molecular pharmacology of metabotropic receptors targeted by neuropsychiatric drugs. Nature Structural & Molecular Biology, 26(7), 535-544. https://doi.org/10.1038/s41594-019-0252-8 Ryves, W. J., & Harwood, A. J. (2001). Lithium inhibits glycogen synthase kinase-3 by competition for magnesium. Biochemical and Biophysical Research Communications, 280(3), 720-725. https://doi.org/10.1006/bbrc.2000.4169 Sánchez Triviño, C. A. (2019). Estudio fisiológico de los efectos del litio sobre la cascada de señalización mediada por la fosfolipasa C en modelos neuronales [Masters, Universidad Nacional de Colombia - Sede Bogotá]. http://bdigital.unal.edu.co/73555/ Sassi, R. B., Nicoletti, M., Brambilla, P., Mallinger, A. G., Frank, E., Kupfer, D. J., Keshavan, M. S., & Soares, J. C. (2002). Increased gray matter volume in lithium-treated bipolar disorder patients. Neuroscience Letters, 329(2), 243-245. https://doi.org/10.1016/s0304-3940(02)00615-8 Satoh, T., Ross, C. A., Villa, A., Supattapone, S., Pozzan, T., Snyder, S. H., & Meldolesi, J. (1990). The inositol 1,4,5,-trisphosphate receptor in cerebellar Purkinje cells: Quantitative immunogold labeling reveals concentration in an ER subcompartment. The Journal of Cell Biology, 111(2), 615-624. https://doi.org/10.1083/jcb.111.2.615 Savitz, J. B., Price, J. L., & Drevets, W. C. (2014). Neuropathological and neuromorphometric abnormalities in bipolar disorder: View from the medial prefrontal cortical network. Neuroscience and Biobehavioral Reviews, 42, 132-147. https://doi.org/10.1016/j.neubiorev.2014.02.008 Schilling, K., Dickinson, M. H., Connor, J. A., & Morgan, J. I. (1991). Electrical activity in cerebellar cultures determines Purkinje cell dendritic growth patterns. Neuron, 7(6), 891-902. https://doi.org/10.1016/0896-6273(91)90335-w Schmidt, H., Stiefel, K. M., Racay, P., Schwaller, B., & Eilers, J. (2003). Mutational analysis of dendritic Ca2+ kinetics in rodent Purkinje cells: Role of parvalbumin and calbindin D28k. The Journal of Physiology, 551(Pt 1), 13-32. https://doi.org/10.1113/jphysiol.2002.035824 Shorter, E. (2009). The history of lithium therapy. Bipolar disorders, 11, 4-9. https://doi.org/10.1111/j.1399-5618.2009.00706.x Smith, F. E., Thelwall, P. E., Necus, J., Flowers, C. J., Blamire, A. M., & Cousins, D. A. (2018). 3D 7Li magnetic resonance imaging of brain lithium distribution in bipolar disorder. Molecular Psychiatry, 23(11), 2184-2191. https://doi.org/10.1038/s41380-018-0016-6 Soboloff, J., Spassova, M., Hewavitharana, T., He, L. P., Luncsford, P., Xu, W., Venkatachalam, K., van Rossum, D., Patterson, R. L., & Gill, D. L. (2007). TRPC channels: Integrators of multiple cellular signals. Handbook of Experimental Pharmacology, 179, 575-591. https://doi.org/10.1007/978-3-540-34891-7_34 Sossin, W. S., & Farah, C. A. (2009). Synaptic Plasticity: Diacylglycerol Signalling role. En L. R. Squire (Ed.), Encyclopedia of Neuroscience (pp. 747-755). Academic Press. https://doi.org/10.1016/B978-008045046-9.00820-2 Sproule, B. A., Hardy, B. G., & Shulman, K. I. (2000). Differential pharmacokinetics of lithium in elderly patients. Drugs & Aging, 16(3), 165-177. https://doi.org/10.2165/00002512-200016030-00002 Staub, C., Vranesic, I., & Knöpfel, T. (1992). Responses to Metabotropic Glutamate Receptor Activation in Cerebellar Purkinje Cells: Induction of an Inward Current. The European Journal of Neuroscience, 4(9), 832-839. https://doi.org/10.1111/j.1460-9568.1992.tb00193.x Stout, J., Hozer, F., Coste, A., Mauconduit, F., Djebrani-Oussedik, N., Sarrazin, S., Poupon, J., Meyrel, M., Romanzetti, S., Etain, B., Rabrait-Lerman, C., Houenou, J., Bellivier, F., Duchesnay, E., & Boumezbeur, F. (2020). Accumulation of Lithium in the Hippocampus of Patients With Bipolar Disorder: A Lithium-7 Magnetic Resonance Imaging Study at 7 Tesla. Biological Psychiatry, 88(5), 426-433. https://doi.org/10.1016/j.biopsych.2020.02.1181 Suh, B.-C., & Hille, B. (2008). PIP2 is a necessary cofactor for ion channel function: How and why? Annual review of biophysics, 37, 175-195. https://doi.org/10.1146/annurev.biophys.37.032807.125859 Suzuki, N., Hajicek, N., & Kozasa, T. (2009). Regulation and physiological functions of G12/13-mediated signaling pathways. Neuro-Signals, 17(1), 55-70. https://doi.org/10.1159/000186690 Syrovatkina, V., Alegre, K. O., Dey, R., & Huang, X.-Y. (2016). Regulation, Signaling, and Physiological Functions of G-Proteins. Journal of Molecular Biology, 428(19), 3850-3868. https://doi.org/10.1016/j.jmb.2016.08.002 Tabata, T., Sawada, S., Araki, K., Bono, Y., Furuya, S., & Kano, M. (2000). A reliable method for culture of dissociated mouse cerebellar cells enriched for Purkinje neurons. Journal of Neuroscience Methods, 104(1), 45-53. https://doi.org/10.1016/s0165-0270(00)00323-x Tanaka, J., Nakagawa, S., Kushiya, E., Yamasaki, M., Fukaya, M., Iwanaga, T., Simon, M. I., Sakimura, K., Kano, M., & Watanabe, M. (2000). Gq protein α subunits Gαq and Gα11 are localized at postsynaptic extra-junctional membrane of cerebellar Purkinje cells and hippocampal pyramidal cells. European Journal of Neuroscience, 12(3), 781-792. https://doi.org/10.1046/j.1460-9568.2000.00959.x Tanaka, M. (2009). Dendrite formation of cerebellar Purkinje cells. Neurochemical Research, 34(12), 2078-2088. https://doi.org/10.1007/s11064-009-0073-y Tempia, F., Alojado, M. E., Strata, P., & Knöpfel, T. (2001). Characterization of the mGluR(1)-mediated electrical and calcium signaling in Purkinje cells of mouse cerebellar slices. Journal of Neurophysiology, 86(3), 1389-1397. https://doi.org/10.1152/jn.2001.86.3.1389 The Human Protein Atlas. (s. f.). Recuperado 8 de marzo de 2021, de https://www.proteinatlas.org/ Thermo Fisher Scientific. (2020). Neurobiology protocol handbook. 136. Timmer, R. T., & Sands, J. M. (1999). Lithium intoxication. Journal of the American Society of Nephrology: JASN, 10(3), 666-674. https://doi.org/10.1681/ASN.V103666 Tjaden, J., Pieczora, L., Wach, F., Theiss, C., & Theis, V. (2018). Cultivation of Purified Primary Purkinje Cells from Rat Cerebella. Cellular and Molecular Neurobiology, 38(7), 1399-1412. https://doi.org/10.1007/s10571-018-0606-5 Tondo, L., Alda, M., Bauer, M., Bergink, V., Grof, P., Hajek, T., Lewitka, U., Licht, R. W., Manchia, M., Müller-Oerlinghausen, B., Nielsen, R. E., Selo, M., Simhandl, C., & Baldessarini, R. J. (2019). Clinical use of lithium salts: Guide for users and prescribers. International Journal of Bipolar Disorders, 7. https://doi.org/10.1186/s40345-019-0151-2 Toselli, M., Masetto, S., Rossi, P., & Taglietti, V. (1991). Characterization of a Voltage-dependent Calcium Current in the Human Neuroblastoma Cell Line SH-SY5Y During Differentiation. The European Journal of Neuroscience, 3(6), 514-522. https://doi.org/10.1111/j.1460-9568.1991.tb00838.x Toselli, M., Tosetti, P., & Taglietti, V. (1996). Functional changes in sodium conductances in the human neuroblastoma cell line SH-SY5Y during in vitro differentiation. Journal of Neurophysiology, 76(6), 3920-3927. https://doi.org/10.1152/jn.1996.76.6.3920 Tosetti, P., Taglietti, V., & Toselli, M. (1998). Functional changes in potassium conductances of the human neuroblastoma cell line SH-SY5Y during in vitro differentiation. Journal of Neurophysiology, 79(2), 648-658. https://doi.org/10.1152/jn.1998.79.2.648 Uhlén, M., Fagerberg, L., Hallström, B. M., Lindskog, C., Oksvold, P., Mardinoglu, A., Sivertsson, Å., Kampf, C., Sjöstedt, E., Asplund, A., Olsson, I., Edlund, K., Lundberg, E., Navani, S., Szigyarto, C. A.-K., Odeberg, J., Djureinovic, D., Takanen, J. O., Hober, S., … Pontén, F. (2015). Proteomics. Tissue-based map of the human proteome. Science (New York, N.Y.), 347(6220), 1260419. https://doi.org/10.1126/science.1260419 Uhlen, M., Oksvold, P., Fagerberg, L., Lundberg, E., Jonasson, K., Forsberg, M., Zwahlen, M., Kampf, C., Wester, K., Hober, S., Wernerus, H., Björling, L., & Ponten, F. (2010). Towards a knowledge-based Human Protein Atlas. Nature Biotechnology, 28(12), 1248-1250. https://doi.org/10.1038/nbt1210-1248 Vazquez, G., Wedel, B. J., Aziz, O., Trebak, M., & Putney, J. W. (2004). The mammalian TRPC cation channels. Biochimica Et Biophysica Acta, 1742(1-3), 21-36. https://doi.org/10.1016/j.bbamcr.2004.08.015 Venkatachalam, K., Zheng, F., & Gill, D. L. (2003). Regulation of canonical transient receptor potential (TRPC) channel function by diacylglycerol and protein kinase C. The Journal of Biological Chemistry, 278(31), 29031-29040. https://doi.org/10.1074/jbc.M302751200 Vetter, I., Mozar, C. A., Durek, T., Wingerd, J. S., Alewood, P. F., Christie, M. J., & Lewis, R. J. (2012). Characterisation of Na(v) types endogenously expressed in human SH-SY5Y neuroblastoma cells. Biochemical Pharmacology, 83(11), 1562-1571. https://doi.org/10.1016/j.bcp.2012.02.022 Vieta, E., Berk, M., Schulze, T. G., Carvalho, A. F., Suppes, T., Calabrese, J. R., Gao, K., Miskowiak, K. W., & Grande, I. (2018). Bipolar disorders. Nature Reviews. Disease Primers, 4, 18008. https://doi.org/10.1038/nrdp.2018.8 Vines, C. M. (2012). Phospholipase C. En Md. S. Islam (Ed.), Calcium Signaling (pp. 235-254). Springer Netherlands. https://doi.org/10.1007/978-94-007-2888-2_10 Walton, P. D., Airey, J. A., Sutko, J. L., Beck, C. F., Mignery, G. A., Südhof, T. C., Deerinck, T. J., & Ellisman, M. H. (1991). Ryanodine and inositol trisphosphate receptors coexist in avian cerebellar Purkinje neurons. The Journal of Cell Biology, 113(5), 1145-1157. https://doi.org/10.1083/jcb.113.5.1145 Wang, H. Y., & Friedman, E. (1999). Effects of lithium on receptor-mediated activation of G proteins in rat brain cortical membranes. Neuropharmacology, 38(3), 403-414. https://doi.org/10.1016/s0028-3908(98)00197-x Whitaker, M. (2006). Calcium at Fertilization and in Early Development. Physiological Reviews, 86(1), 25-88. https://doi.org/10.1152/physrev.00023.2005 Womack, M. D., Walker, J. W., & Khodakhah, K. (2000). Impaired calcium release in cerebellar Purkinje neurons maintained in culture. The Journal of General Physiology, 115(3), 339-346. https://doi.org/10.1085/jgp.115.3.339 Worley, P. F., Baraban, J. M., & Snyder, S. H. (1989). Inositol 1,4,5-trisphosphate receptor binding: Autoradiographic localization in rat brain. The Journal of Neuroscience: The Official Journal of the Society for Neuroscience, 9(1), 339-346. Yamakawa, Y., & Hirano, T. (1999). Contribution of mGluR1 to the basal activity of a mouse cerebellar Purkinje neuron. Neuroscience Letters, 277(2), 103-106. https://doi.org/10.1016/s0304-3940(99)00852-6 Yuzaki, M., & Mikoshiba, K. (1992). Pharmacological and immunocytochemical characterization of metabotropic glutamate receptors in cultured Purkinje cells. Journal of Neuroscience, 12(11), 4253-4263. https://doi.org/10.1523/JNEUROSCI.12-11-04253.1992 Zhang, C., Zhu, Q., & Hua, T. (2010). Aging of cerebellar Purkinje cells. Cell and Tissue Research, 341(3), 341-347. https://doi.org/10.1007/s00441-010-1016-2 |
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Atribución-NoComercial-SinDerivadas 4.0 Internacionalhttp://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccesshttp://purl.org/coar/access_right/c_abf2Gómez Correa, María del Pilar69446e21238a4cfcfe3166184ed45e6bNasi Lignarolo, Enricob880efc08f05d0579d6f076cca5dd9cdMantilla Esparza, Fabián Andréscdb22f90cad797181544670057e3c56aBiofísica de la Señalización Celular2022-03-02T20:09:50Z2022-03-02T20:09:50Z2021https://repositorio.unal.edu.co/handle/unal/81116Universidad Nacional de ColombiaRepositorio Institucional Universidad Nacional de Colombiahttps://repositorio.unal.edu.co/ilustraciones, fotografías, gráficasEl litio se ha usado por décadas como estabilizador del estado de ánimo en trastornos bipolares, pero sus mecanismos de acción a nivel celular aun no se han esclarecido. Aproximaciones bioquímicas resaltan la importancia, entre otras, de la vía de los fosfoinositoles. Nuestro laboratorio reportó efectos potenciadores del litio sobre la movilización de calcio intracelular y corrientes de membrana evocadas por activación de la vía de la fosfolipasa C (PLC) en líneas celulares: el sitio de acción fue acotado a la interacción entre proteína Gq y PLC. La existencia de variadas isoformas de estas proteínas en el sistema nervioso hace pertinente estudiar la generalidad de estos hallazgos en neuronas primarias. En el presente trabajo se implementó un cultivo de neuronas de cerebelo, ya que las neuronas de Purkinje expresan masivamente receptores de IP3 y distintas isoformas de PLC. Por razones de costo y fácil acceso, se utilizaron embriones de pollo. La selección de células candidatas se realizó mediante criterios morfológicos complementados por registros de ‘whole-cell voltage clamp’ que mostraron corrientes capacitivas lentas y de gran magnitud. Su viabilidad fue corroborada por la presencia de corrientes tanto voltaje-dependientes como activadas por quisquilato, un agonista de receptores glutamatérgicos acoplados a Gq/PLC. El quisquilato indujo además incrementos de calcio citosólico, provenientes en parte de reservorios intracelulares y sensibles a inhibición de la PLC. Finalmente, la exposición aguda a litio indujo reducción o potenciación de la respuesta de calcio en distintas células, sugiriendo un efecto diferencial del litio sobre variantes moleculares de PLC y/o Gq. (Texto tomado de la fuente).Lithium has been used for decades as a mood stabilizer in bipolar disorder, but its mechanisms of action at cellular level have not been clarified yet. Biochemical approaches highlight the importance, among others, of the phosphoinositides pathway. Our laboratory reported potentiating effects of lithium over the intracellular calcium mobilization and membrane currents evoked by the activation of the Phospholipase C (PLC) pathway in cell lines: the site of action was narrowed down to the interaction between the Gq protein and the PLC. The existence of diverse isoforms of these proteins in the nervous system makes pertinent to study the generality of these findings in primary neurons. In the present work a cerebellar neuronal culture was implemented, given that Purkinje neurons massively express IP3 receptors and diverse isoforms of PLC. Chick embryos were used for reasons of cost and easy access. The selection of candidate neurons was made by morphological criteria complemented by whole-cell voltage clamp recordings that showed slow capacitive currents with big amplitude. Cell viability was corroborated by the presence voltage-dependent currents as well as currents activated by quisqualate, an agonist of glutamatergic receptors coupled to Gq/PLC. Quisqualate induced cytosolic calcium increments, originated in part from intracellular reservoirs, and sensitive to PLC inhibition. Finally, exposure to acute lithium induced reduction or potentiation of the calcium response in different cells, suggesting a differential effect of lithium over molecular variants of PLC and/or Gq.MaestríaMagíster en Ciencias - BiologíaNeurofisiología celularxvi, 80 páginasapplication/pdfspaUniversidad Nacional de ColombiaBogotá - Ciencias - Maestría en Ciencias - BiologíaDepartamento de BiologíaFacultad de CienciasBogotá, ColombiaUniversidad Nacional de Colombia - Sede Bogotá570 - Biología::571 - Fisiología y temas relacionadosEnzymesPurkinje CellsEnzimasCélulas de PurkinjeNeuronsNeuronasLitioCélula de PurkinjeTrastorno bipolarEmbrión de polloProteína GqCultivo celular primarioFosfolipasa CLithiumPurkinje cellBipolar disorderChick embryoGq proteinPrimary cell culturePhospholipase CImplementación de un cultivo neuronal primario como modelo para el estudio de mecanismos de modulación sobre la vía de señalización de los fosfoinositolesImplementation of a primary neuronal culture as a model for the study of modulatory mechanisms on the phosphoinositide signaling pathwayTrabajo de grado - Maestríainfo:eu-repo/semantics/masterThesisinfo:eu-repo/semantics/acceptedVersionTexthttp://purl.org/redcol/resource_type/TMAche, B. W., & Young, J. M. (2005). Olfaction: Diverse Species, Conserved Principles. Neuron, 48(3), 417-430. https://doi.org/10.1016/j.neuron.2005.10.022Aiba, A., Kano, M., Chen, C., Stanton, M. E., Fox, G. D., Herrup, K., Zwingman, T. A., & Tonegawa, S. (1994). Deficient cerebellar long-term depression and impaired motor learning in mGluR1 mutant mice. Cell, 79(2), 377-388.Akar, S., & Sur, E. (2010). The development of chicken cerebellar cortex and the determination of AgNOR activity of the Purkinje cell nuclei. Belgian Journal of Zoology, 140.Allison, J. H., & Stewart, M. A. (1971). Reduced brain inositol in lithium-treated rats. Nature: New Biology, 233(43), 267-268. https://doi.org/10.1038/newbio233267a0Aloulou, A., Rahier, R., Arhab, Y., Noiriel, A., & Abousalham, A. (2018). Phospholipases: An Overview. Methods in Molecular Biology (Clifton, N.J.), 1835, 69-105. https://doi.org/10.1007/978-1-4939-8672-9_3Angueyra, J. M., Pulido, C., Malagón, G., Nasi, E., & Gomez, M. del P. (2012). Melanopsin-Expressing Amphioxus Photoreceptors Transduce Light via a Phospholipase C Signaling Cascade. PLoS ONE, 7(1), e29813. https://doi.org/10.1371/journal.pone.0029813Ardeshiri, A., Kelley, M. H., Korner, I. P., Hurn, P. D., & Herson, P. S. (2006). Mechanism of progesterone neuroprotection of rat cerebellar Purkinje cells following oxygen–glucose deprivation. European Journal of Neuroscience, 24(9), 2567-2574. https://doi.org/10.1111/j.1460-9568.2006.05142.xArora, M. (2013). Cell Culture Media: A Review. MATER METHODS, 3(175), 24. https://doi.org///dx.doi.org/10.13070/mm.en.3.175Audinat, E., Knöpfel, T., & Gähwiler, B. H. (1990). Responses to excitatory amino acids of Purkinje cells’ and neurones of the deep nuclei in cerebellar slice cultures. The Journal of Physiology, 430, 297-313. https://doi.org/10.1113/jphysiol.1990.sp018292Avissar, S., Murphy, D. L., & Schreiber, G. (1991). Magnesium reversal of lithium inhibition of beta-adrenergic and muscarinic receptor coupling to G proteins. Biochemical Pharmacology, 41(2), 171-175. https://doi.org/10.1016/0006-2952(91)90473-iAvissar, S., & Schreiber, G. (1992). The involvement of guanine nucleotide binding proteins in the pathogenesis and treatment of affective disorders. Biological Psychiatry, 31(5), 435-459. https://doi.org/10.1016/0006-3223(92)90257-zAvissar, S., Schreiber, G., Danon, A., & Belmaker, R. H. (1988). Lithium inhibits adrenergic and cholinergic increases in GTP binding in rat cortex. Nature, 331(6155), 440-442. https://doi.org/10.1038/331440a0Báez-Becerra, C., Filipello, F., Sandoval-Hernández, A., Arboleda, H., & Arboleda, G. (2018). Liver X Receptor Agonist GW3965 Regulates Synaptic Function upon Amyloid Beta Exposure in Hippocampal Neurons. Neurotoxicity Research, 33(3), 569-579. https://doi.org/10.1007/s12640-017-9845-3Baptista, C. A., Hatten, M. E., Blazeski, R., & Mason, C. A. (1994). Cell-cell interactions influence survival and differentiation of purified Purkinje cells in vitro. Neuron, 12(2), 243-260. https://doi.org/10.1016/0896-6273(94)90268-2Bastianelli, E., & Pochet, R. (1993). Transient expression of calretinin during development of chick cerebellum. Comparison with calbindin-D28k. Neuroscience Research, 17(1), 53-61. https://doi.org/10.1016/0168-0102(93)90029-pBatchelor, A. M., Madge, D. J., & Garthwaite, J. (1994). Synaptic activation of metabotropic glutamate receptors in the parallel fibre-Purkinje cell pathway in rat cerebellar slices. Neuroscience, 63(4), 911-915. https://doi.org/10.1016/0306-4522(94)90558-4Bearden, C. E., Thompson, P. M., Dalwani, M., Hayashi, K. M., Lee, A. D., Nicoletti, M., Trakhtenbroit, M., Glahn, D. C., Brambilla, P., Sassi, R. B., Mallinger, A. G., Frank, E., Kupfer, D. J., & Soares, J. C. (2007). Greater cortical gray matter density in lithium-treated patients with bipolar disorder. Biological Psychiatry, 62(1), 7-16. https://doi.org/10.1016/j.biopsych.2006.10.027Berk, M., Dodd, S., Kauer-Sant’anna, M., Malhi, G. S., Bourin, M., Kapczinski, F., & Norman, T. (2007). Dopamine dysregulation syndrome: Implications for a dopamine hypothesis of bipolar disorder. Acta Psychiatrica Scandinavica. Supplementum, 434, 41-49. https://doi.org/10.1111/j.1600-0447.2007.01058.xBerridge, M. J., Downes, C. P., & Hanley, M. R. (1989). Neural and developmental actions of lithium: A unifying hypothesis. Cell, 59(3), 411-419. https://doi.org/10.1016/0092-8674(89)90026-3Berridge, M. J., & Irvine, R. F. (1984). Inositol trisphosphate, a novel second messenger in cellular signal transduction. Nature, 312(5992), 315-321. https://doi.org/10.1038/312315a0Bertossi, M., Roncali, L., Mancini, L., Ribatti, D., & Nico, B. (1986). Process of differentiation of cerebellar Purkinje neurons in the chick embryo. Anatomy and Embryology, 175(1), 25-34. https://doi.org/10.1007/BF00315453Beurel, E., & Jope, R. S. (2006). The paradoxical pro- and anti-apoptotic actions of GSK3 in the intrinsic and extrinsic apoptosis signaling pathways. Progress in Neurobiology, 79(4), 173-189. https://doi.org/10.1016/j.pneurobio.2006.07.006Bezprozvanny, L., Watras, J., & Ehrlich, B. E. (1991). Bell-shaped calcium-response curves of lns(l,4,5)P 3—And calcium-gated channels from endoplasmic reticulum of cerebellum. Nature, 351(6329), 751-754. https://doi.org/10.1038/351751a0Brorson, J. R., Bleakman, D., Gibbons, S. J., & Miller, R. J. (1991). The properties of intracellular calcium stores in cultured rat cerebellar neurons. The Journal of Neuroscience: The Official Journal of the Society for Neuroscience, 11(12), 4024-4043.Butler-Munro, C., Coddington, E. J., Shirley, C. H., & Heyward, P. M. (2010). Lithium modulates cortical excitability in vitro. Brain Research, 1352, 50-60. https://doi.org/10.1016/j.brainres.2010.07.021Caraux, A., Kim, N., Bell, S. E., Zompi, S., Ranson, T., Lesjean-Pottier, S., Garcia-Ojeda, M. E., Turner, M., & Colucci, F. (2006). Phospholipase C-γ2 is essential for NK cell cytotoxicity and innate immunity to malignant and virally infected cells. Blood, 107(3), 994-1002. https://doi.org/10.1182/blood-2005-06-2428Carli, M., Anand-Srivastava, M. B., Molina-Holgado, E., Dewar, K. M., & Reader, T. A. (1994). Effects of chronic lithium treatments on central dopaminergic receptor systems: G proteins as possible targets. Neurochemistry International, 24(1), 13-22. https://doi.org/10.1016/0197-0186(94)90124-4Casebolt, T. L., & Jope, R. S. (1987). Chronic lithium treatment reduces norepinephrine-stimulated inositol phospholipid hydrolysis in rat cortex. European Journal of Pharmacology, 140(2), 245-246. https://doi.org/10.1016/0014-2999(87)90813-2Clapham, D. E. (2007). Calcium Signaling. Cell, 131(6), 1047-1058. https://doi.org/10.1016/j.cell.2007.11.028Cohen-Cory, S., Dreyfus, C. F., & Black, I. B. (1991). NGF and excitatory neurotransmitters regulate survival and morphogenesis of cultured cerebellar Purkinje cells. The Journal of Neuroscience: The Official Journal of the Society for Neuroscience, 11(2), 462-471.Conquet, F., Bashir, Z. I., Davies, C. H., Daniel, H., Ferraguti, F., Bordi, F., Franz-Bacon, K., Reggiani, A., Matarese, V., & Condé, F. (1994). Motor deficit and impairment of synaptic plasticity in mice lacking mGluR1. Nature, 372(6503), 237-243. https://doi.org/10.1038/372237a0Consalez, G. G., Goldowitz, D., Casoni, F., & Hawkes, R. (2020). Origins, Development, and Compartmentation of the Granule Cells of the Cerebellum. Frontiers in Neural Circuits, 14, 611841. https://doi.org/10.3389/fncir.2020.611841Davies, J. A. (2007). Metabotropic Glutamate Receptor Agents. En S. J. Enna & D. B. Bylund (Eds.), XPharm: The Comprehensive Pharmacology Reference (pp. 1-2). Elsevier. https://doi.org/10.1016/B978-008055232-3.60987-0Dixon, J. F., & Hokin, L. E. (1998). Lithium acutely inhibits and chronically up-regulates and stabilizes glutamate uptake by presynaptic nerve endings in mouse cerebral cortex. Proceedings of the National Academy of Sciences of the United States of America, 95(14), 8363-8368. https://doi.org/10.1073/pnas.95.14.8363Durán Ferro, S. (2016). Inmunodetección de las proteínas de la cascada de fosfoinositoles en células HEK293 y evaluación de los efectos del litio sobre corrientes de membrana activadas por esta vía [Tesis de Maestría, Universidad Nacional de Colombia - Sede Bogotá]. https://repositorio.unal.edu.co/handle/unal/59178Dzubay, J. A., & Otis, T. S. (2002). Climbing fiber activation of metabotropic glutamate receptors on cerebellar purkinje neurons. Neuron, 36(6), 1159-1167. https://doi.org/10.1016/s0896-6273(02)01052-8Empson, R. M., & Knöpfel, T. (2012). Functional integration of calcium regulatory mechanisms at Purkinje neuron synapses. Cerebellum (London, England), 11(3), 640-650. https://doi.org/10.1007/s12311-010-0185-6Faber, E. S. L., Sedlak, P., Vidovic, M., & Sah, P. (2006). Synaptic activation of transient receptor potential channels by metabotropic glutamate receptors in the lateral amygdala. Neuroscience, 137(3), 781-794. https://doi.org/10.1016/j.neuroscience.2005.09.027Fain, G. L., Hardie, R., & Laughlin, S. B. (2010). Phototransduction and the Evolution of Photoreceptors. Current Biology, 20(3), R114-R124. https://doi.org/10.1016/j.cub.2009.12.006Fleming, J. T., He, W., Hao, C., Ketova, T., Pan, F. C., Wright, C. C. V., Litingtung, Y., & Chiang, C. (2013). The Purkinje Neuron Acts as a Central Regulator of Spatially and Functionally Distinct Cerebellar Precursors. Developmental Cell, 27(3), 278-292. https://doi.org/10.1016/j.devcel.2013.10.008Foelix, R. F., & Oppenheim, R. (1974). The development of synapses in the cerebellar cortex of the chick embryo. Journal of Neurocytology, 3(3), 277-294. https://doi.org/10.1007/BF01097914Forsythe, I. D., Lambert, D. G., Nahorski, S. R., & Lindsdell, P. (1992). Elevation of cytosolic calcium by cholinoceptor agonists in SH-SY5Y human neuroblastoma cells: Estimation of the contribution of voltage-dependent currents. British Journal of Pharmacology, 107(1), 207-214. https://doi.org/10.1111/j.1476-5381.1992.tb14488.xFountoulakis, K. N., Vieta, E., Sanchez-Moreno, J., Kaprinis, S. G., Goikolea, J. M., & Kaprinis, G. S. (2005). Treatment guidelines for bipolar disorder: A critical review. Journal of Affective Disorders, 86(1), 1-10. https://doi.org/10.1016/j.jad.2005.01.004Fujishima, K., Horie, R., Mochizuki, A., & Kengaku, M. (2012). Principles of branch dynamics governing shape characteristics of cerebellar Purkinje cell dendrites. Development, 139(18), 3442-3455. https://doi.org/10.1242/dev.081315Fujishima, K., Kawabata Galbraith, K., & Kengaku, M. (2018). Dendritic Self-Avoidance and Morphological Development of Cerebellar Purkinje Cells. Cerebellum (London, England), 17(6), 701-708. https://doi.org/10.1007/s12311-018-0984-8Fukami, K., Inanobe, S., Kanemaru, K., & Nakamura, Y. (2010). Phospholipase C is a key enzyme regulating intracellular calcium and modulating the phosphoinositide balance. Progress in Lipid Research, 49(4), 429-437. https://doi.org/10.1016/j.plipres.2010.06.001Fukumoto, T., Morinobu, S., Okamoto, Y., Kagaya, A., & Yamawaki, S. (2001). Chronic lithium treatment increases the expression of brain-derived neurotrophic factor in the rat brain. Psychopharmacology, 158(1), 100-106. https://doi.org/10.1007/s002130100871Furuya, S., Makino, A., & Hirabayashi, Y. (1998). An improved method for culturing cerebellar Purkinje cells with differentiated dendrites under a mixed monolayer setting. Brain Research. Brain Research Protocols, 3(2), 192-198. https://doi.org/10.1016/s1385-299x(98)00040-3Geddes, J. R., & Miklowitz, D. J. (2013). Treatment of bipolar disorder. The Lancet, 381(9878), 1672-1682. https://doi.org/10.1016/S0140-6736(13)60857-0Giussani, D. A., Salinas, C. E., Villena, M., & Blanco, C. E. (2007). The role of oxygen in prenatal growth: Studies in the chick embryo. The Journal of Physiology, 585(Pt 3), 911-917. https://doi.org/10.1113/jphysiol.2007.141572Godfrey, P. P., McClue, S. J., White, A. M., Wood, A. J., & Grahame-Smith, D. G. (1989). Subacute and chronic in vivo lithium treatment inhibits agonist- and sodium fluoride-stimulated inositol phosphate production in rat cortex. Journal of Neurochemistry, 52(2), 498-506. https://doi.org/10.1111/j.1471-4159.1989.tb09148.xGomez, L. C., Kawaguchi, S.-Y., Collin, T., Jalil, A., Gomez, M. D. P., Nasi, E., Marty, A., & Llano, I. (2020). Influence of spatially segregated IP3-producing pathways on spike generation and transmitter release in Purkinje cell axons. Proceedings of the National Academy of Sciences of the United States of America, 117(20), 11097-11108. https://doi.org/10.1073/pnas.2000148117Grande, I., Berk, M., Birmaher, B., & Vieta, E. (2016). Bipolar disorder. The Lancet, 387(10027), 1561-1572. https://doi.org/10.1016/S0140-6736(15)00241-XGrimes, C. A., & Jope, R. S. (2001). The multifaceted roles of glycogen synthase kinase 3beta in cellular signaling. Progress in Neurobiology, 65(4), 391-426. https://doi.org/10.1016/s0301-0082(01)00011-9Grunze, H., Vieta, E., Goodwin, G. M., Bowden, C., Licht, R. W., Azorin, J.-M., Yatham, L., Mosolov, S., Möller, H.-J., Kasper, S., & Members of the WFSBP Task Force on Bipolar Affective Disorders Working on this topic. (2018). The World Federation of Societies of Biological Psychiatry (WFSBP) Guidelines for the Biological Treatment of Bipolar Disorders: Acute and long-term treatment of mixed states in bipolar disorder. The World Journal of Biological Psychiatry: The Official Journal of the World Federation of Societies of Biological Psychiatry, 19(1), 2-58. https://doi.org/10.1080/15622975.2017.1384850Hallcher, L. M., & Sherman, W. R. (1980). The effects of lithium ion and other agents on the activity of myo-inositol-1-phosphatase from bovine brain. The Journal of Biological Chemistry, 255(22), 10896-10901.Hamburger, V., & Hamilton, H. L. (1951). A series of normal stages in the development of the chick embryo. Journal of Morphology, 88(1), 49-92. https://doi.org/10.1002/jmor.1050880104Harrison, P. J., Geddes, J. R., & Tunbridge, E. M. (2018). The Emerging Neurobiology of Bipolar Disorder. Trends in Neurosciences, 41(1), 18-30. https://doi.org/10.1016/j.tins.2017.10.006Hartmann, J., & Konnerth, A. (2009). Mechanisms of metabotropic glutamate receptor-mediated synaptic signalling in cerebellar Purkinje cells. Acta Physiologica, 195(1), 79-90. https://doi.org/10.1111/j.1748-1716.2008.01923.xHeintz, T. G., Eva, R., & Fawcett, J. W. (2016). Regional Regulation of Purkinje Cell Dendritic Spines by Integrins and Eph/Ephrins. PLOS ONE, 11(8), e0158558. https://doi.org/10.1371/journal.pone.0158558Hibar, D. P., Westlye, L. T., Doan, N. T., Jahanshad, N., Cheung, J. W., Ching, C. R. K., Versace, A., Bilderbeck, A. C., Uhlmann, A., Mwangi, B., Krämer, B., Overs, B., Hartberg, C. B., Abé, C., Dima, D., Grotegerd, D., Sprooten, E., Bøen, E., Jimenez, E., … Andreassen, O. A. (2018). Cortical abnormalities in bipolar disorder: An MRI analysis of 6503 individuals from the ENIGMA Bipolar Disorder Working Group. Molecular Psychiatry, 23(4), 932-942. https://doi.org/10.1038/mp.2017.73Hibar, D. P., Westlye, L. T., van Erp, T. G. M., Rasmussen, J., Leonardo, C. D., Faskowitz, J., Haukvik, U. K., Hartberg, C. B., Doan, N. T., Agartz, I., Dale, A. M., Gruber, O., Krämer, B., Trost, S., Liberg, B., Abé, C., Ekman, C. J., Ingvar, M., Landén, M., … Andreassen, O. A. (2016). Subcortical volumetric abnormalities in bipolar disorder. Molecular Psychiatry, 21(12), 1710-1716. https://doi.org/10.1038/mp.2015.227Hilgemann, D. W. (2007). On the physiological roles of PIP2 at cardiac Na+–Ca2+ exchangers and KATP channels: A long journey from membrane biophysics into cell biology. The Journal of Physiology, 582(Pt 3), 903-909. https://doi.org/10.1113/jphysiol.2007.132746Hinoi, E., Ogita, K., Takeuchi, Y., Ohashi, H., Maruyama, T., & Yoneda, Y. (2001). Characterization with [3H]quisqualate of group I metabotropic glutamate receptor subtype in rat central and peripheral excitable tissues. Neurochemistry International, 38(3), 277-285. https://doi.org/10.1016/s0197-0186(00)00075-9Hirano, T. (2018). Regulation and Interaction of Multiple Types of Synaptic Plasticity in a Purkinje Neuron and Their Contribution to Motor Learning. Cerebellum (London, England), 17(6), 756-765. https://doi.org/10.1007/s12311-018-0963-0Hirano, T., & Hagiwara, S. (1989). Kinetics and distribution of voltage-gated Ca, Na and K channels on the somata of rat cerebellar Purkinje cells. Pflugers Archiv: European Journal of Physiology, 413(5), 463-469. https://doi.org/10.1007/BF00594174Hockberger, P. E., Tseng, H. Y., & Connor, J. A. (1989a). Development of rat cerebellar Purkinje cells: Electrophysiological properties following acute isolation and in long-term culture. The Journal of Neuroscience: The Official Journal of the Society for Neuroscience, 9(7), 2258-2271.Hockberger, P. E., Tseng, H. Y., & Connor, J. A. (1989b). Development of rat cerebellar Purkinje cells: Electrophysiological properties following acute isolation and in long-term culture. The Journal of Neuroscience: The Official Journal of the Society for Neuroscience, 9(7), 2258-2271.Huang, C.-L. (2007). Complex roles of PIP2 in the regulation of ion channels and transporters. American Journal of Physiology. Renal Physiology, 293(6), F1761-1765. https://doi.org/10.1152/ajprenal.00400.2007Hurowitz, E. H., Melnyk, J. M., Chen, Y.-J., Kouros-Mehr, H., Simon, M. I., & Shizuya, H. (2000). Genomic Characterization of the Human Heterotrimeric G Protein α, β, and γ Subunit Genes. DNA Research, 7(2), 111-120. https://doi.org/10.1093/dnares/7.2.111Hussain, S., Gardner, C. R., Bagust, J., & Walker, R. J. (1991). Receptor sub-types involved in responses of Purkinje cell to exogenous excitatory amino acids and local electrical stimulation in cerebellar slices in the rat. Neuropharmacology, 30(10), 1029-1037. https://doi.org/10.1016/0028-3908(91)90130-4Ichise, T., Kano, M., Hashimoto, K., Yanagihara, D., Nakao, K., Shigemoto, R., Katsuki, M., & Aiba, A. (2000). MGluR1 in Cerebellar Purkinje Cells Essential for Long-Term Depression, Synapse Elimination, and Motor Coordination. Science, 288(5472), 1832-1835. https://doi.org/10.1126/science.288.5472.1832Ito, M. (1987). Signal processing in cerebellar Purkinje cells. Physiologia Bohemoslovaca, 36(3), 203-216.Ito, M. (2001). Cerebellar Long-Term Depression: Characterization, Signal Transduction, and Functional Roles. Physiological Reviews, 81(3), 1143-1195. https://doi.org/10.1152/physrev.2001.81.3.1143Ito, M. (2002). Historical review of the significance of the cerebellum and the role of Purkinje cells in motor learning. Annals of the New York Academy of Sciences, 978, 273-288. https://doi.org/10.1111/j.1749-6632.2002.tb07574.xIto, M., & Karachot, L. (1990). Messengers mediating long-term desensitization in cerebellar Purkinje cells. Neuroreport, 1(2), 129-132. https://doi.org/10.1097/00001756-199010000-00012Itsuki, K., Imai, Y., Hase, H., Okamura, Y., Inoue, R., & Mori, M. X. (2014). PLC-mediated PI(4,5)P2 hydrolysis regulates activation and inactivation of TRPC6/7 channels. The Journal of General Physiology, 143(2), 183-201. https://doi.org/10.1085/jgp.201311033Jeffrey, P. L., Meaney, J., Tolhurst, O., & Weinberger, R. P. (1996). Epigenetic factors controlling the development of avian Purkinje neurons. Journal of Neuroscience Methods, 67(2), 163-175.Jope, R. S. (1999). Anti-bipolar therapy: Mechanism of action of lithium. Molecular Psychiatry, 4(2), 117-128. https://doi.org/10.1038/sj.mp.4000494Jope, R. S. (2003). Lithium and GSK-3: One inhibitor, two inhibitory actions, multiple outcomes. Trends in Pharmacological Sciences, 24(9), 441-443. https://doi.org/10.1016/S0165-6147(03)00206-2Jope, R. S., & Williams, M. B. (1994). Lithium and brain signal transduction systems. Biochemical Pharmacology, 47(3), 429-441. https://doi.org/10.1016/0006-2952(94)90172-4Kadamur, G., & Ross, E. M. (2013). Mammalian Phospholipase C. Annual Review of Physiology, 75(1), 127-154. https://doi.org/10.1146/annurev-physiol-030212-183750Kandel, E. R., Schwartz, J. H., Jessell, T. M., Siegelbaum, S. A., & Hudspeth, A. J. (Eds.). (2012). Principles of Neural Science.Kano, M., & Kato, M. (1987a). Quisqualate receptors are specifically involved in cerebellar synaptic plasticity. Nature, 325(6101), 276-279. https://doi.org/10.1038/325276a0Kano, M., & Kato, M. (1987b). Quisqualate receptors are specifically involved in cerebellar synaptic plasticity. Nature, 325(6101), 276-279. https://doi.org/10.1038/325276a0Kapfhammer, J. P. (2004). Cellular and molecular control of dendritic growth and development of cerebellar Purkinje cells. Progress in Histochemistry and Cytochemistry, 39(3), 131-182. https://doi.org/10.1016/j.proghi.2004.07.002Kendall, D. A., & Nahorski, S. R. (1987). Acute and chronic lithium treatments influence agonist and depolarization-stimulated inositol phospholipid hydrolysis in rat cerebral cortex. The Journal of Pharmacology and Experimental Therapeutics, 241(3), 1023-1027.Kim, D., Jun, K. S., Lee, S. B., Kang, N.-G., Min, D. S., Kim, Y.-H., Ryu, S. H., Suh, P.-G., & Shin, H.-S. (1997). Phospholipase C isozymes selectively couple to specific neurotransmitter receptors. Nature, 389(6648), 290-293. https://doi.org/10.1038/38508Kitamura, K., & Kano, M. (2013). Dendritic calcium signaling in cerebellar Purkinje cell. Neural Networks: The Official Journal of the International Neural Network Society, 47, 11-17. https://doi.org/10.1016/j.neunet.2012.08.001Knöpfel, T., Anchisi, D., Alojado, M. E., Tempia, F., & Strata, P. (2000). Elevation of intradendritic sodium concentration mediated by synaptic activation of metabotropic glutamate receptors in cerebellar Purkinje cells. The European Journal of Neuroscience, 12(6), 2199-2204. https://doi.org/10.1046/j.1460-9568.2000.00122.xKnöpfel, T., & Grandes, P. (2002). Metabotropic glutamate receptors in the cerebellum with a focus on their function in Purkinje cells. Cerebellum (London, England), 1(1), 19-26. https://doi.org/10.1007/BF02941886Lambert, D. G., & Nahorski, S. R. (1990). Muscarinic-receptor-mediated changes in intracellular Ca2+ and inositol 1,4,5-trisphosphate mass in a human neuroblastoma cell line, SH-SY5Y. The Biochemical Journal, 265(2), 555-562. https://doi.org/10.1042/bj2650555Landinez Macias, M. P. (2016). Evaluación fisiológica de los efectos del litio sobre la movilización de calcio intracelular en la línea celular HEK 293 [Tesis de Maestría, Universidad Nacional de Colombia - Sede Bogotá]. https://repositorio.unal.edu.co/handle/unal/56608Lee, C. H., Park, D., Wu, D., Rhee, S. G., & Simon, M. I. (1992). Members of the Gq alpha subunit gene family activate phospholipase C beta isozymes. Journal of Biological Chemistry, 267(23), 16044-16047.Lindemann, B. (2001). Receptors and transduction in taste. Nature, 413(6852), 219-225. https://doi.org/10.1038/35093032Linden, D. J., Dickinson, M. H., Smeyne, M., & Connor, J. A. (1991). A long-term depression of AMPA currents in cultured cerebellar Purkinje neurons. Neuron, 7(1), 81-89. https://doi.org/10.1016/0896-6273(91)90076-cLinden, D. J., Smeyne, M., & Connor, J. A. (1994). Trans-ACPD, a metabotropic receptor agonist, produces calcium mobilization and an inward current in cultured cerebellar Purkinje neurons. Journal of Neurophysiology, 71(5), 1992-1998. https://doi.org/10.1152/jn.1994.71.5.1992Livingstone, C., & Rampes, H. (2006). Lithium: A review of its metabolic adverse effects. Journal of Psychopharmacology, 20(3), 347-355. https://doi.org/10.1177/0269881105057515Llano, I., Dreessen, J., Kano, M., & Konnerth, A. (1991). Intradendritic release of calcium induced by glutamate in cerebellar Purkinje cells. Neuron, 7(4), 577-583. https://doi.org/10.1016/0896-6273(91)90370-fLlinás, R., & Sugimori, M. (1980). Electrophysiological properties of in vitro Purkinje cell somata in mammalian cerebellar slices. The Journal of Physiology, 305, 171-195.Lydiard, R. B., & Gelenberg, A. J. (1982). Hazards and adverse effects of lithium. Annual Review of Medicine, 33, 327-344. https://doi.org/10.1146/annurev.me.33.020182.001551Malhi, G. S., Adams, D., & Berk, M. (2009). Is lithium in a class of its own? A brief profile of its clinical use. The Australian and New Zealand Journal of Psychiatry, 43(12), 1096-1104. https://doi.org/10.3109/00048670903279937Malhi, G. S., & Tanious, M. (2011). Optimal frequency of lithium administration in the treatment of bipolar disorder: Clinical and dosing considerations. CNS Drugs, 25(4), 289-298. https://doi.org/10.2165/11586970-000000000-00000Malhi, G. S., Tanious, M., Das, P., Coulston, C. M., & Berk, M. (2013). Potential Mechanisms of Action of Lithium in Bipolar Disorder. CNS Drugs, 27(2), 135-153. https://doi.org/10.1007/s40263-013-0039-0Marcaggi, P. (2015). Cerebellar endocannabinoids: Retrograde signaling from purkinje cells. Cerebellum (London, England), 14(3), 341-353. https://doi.org/10.1007/s12311-014-0629-5Masana, M. I., Bitran, J. A., Hsiao, J. K., & Potter, W. Z. (1992). In vivo evidence that lithium inactivates Gi modulation of adenylate cyclase in brain. Journal of Neurochemistry, 59(1), 200-205. https://doi.org/10.1111/j.1471-4159.1992.tb08891.xMathews, R., Li, P. P., Young, L. T., Kish, S. J., & Warsh, J. J. (1997). Increased Gαq/11 immunoreactivity in postmortem occipital cortex from patients with bipolar affective disorder. Biological Psychiatry, 41(6), 649-656. https://doi.org/10.1016/S0006-3223(96)00113-8Mayer, M. L., Crunelli, V., & Kemp, J. A. (1984). Lithium ions increase action potential duration of mammalian neurons. Brain Research, 293(1), 173-177. https://doi.org/10.1016/0006-8993(84)91466-5McKay, B. E., & Turner, R. W. (2005). Physiological and morphological development of the rat cerebellar Purkinje cell. The Journal of Physiology, 567(Pt 3), 829-850. https://doi.org/10.1113/jphysiol.2005.089383McKnight, R. F., Adida, M., Budge, K., Stockton, S., Goodwin, G. M., & Geddes, J. R. (2012). Lithium toxicity profile: A systematic review and meta-analysis. The Lancet, 379(9817), 721-728. https://doi.org/10.1016/S0140-6736(11)61516-XMeaney, J. A., Balcar, V. J., Rothstein, J. D., & Jeffrey, P. L. (1998). Glutamate transport in cultures from developing avian cerebellum: Presence of GLT-1 immunoreactivity in Purkinje neurons. Journal of Neuroscience Research, 54(5), 595-603. https://doi.org/10.1002/(SICI)1097-4547(19981201)54:5<595::AID-JNR4>3.0.CO;2-QMei, L., Yamamura, H. I., & Roeske, W. R. (1988). Muscarinic receptor-mediated hydrolysis of phosphatidylinositols in human neuroblastoma (SH-SY5Y) cells is sensitive to pertussis toxin. Brain Research, 447(2), 360-363. https://doi.org/10.1016/0006-8993(88)91140-7Michael, N., Erfurth, A., Ohrmann, P., Gössling, M., Arolt, V., Heindel, W., & Pfleiderer, B. (2003). Acute mania is accompanied by elevated glutamate/glutamine levels within the left dorsolateral prefrontal cortex. Psychopharmacology, 168(3), 344-346. https://doi.org/10.1007/s00213-003-1440-zMilligan, G., & Kostenis, E. (2006). Heterotrimeric G-proteins: A short history. British Journal of Pharmacology, 147(S1), S46-S55. https://doi.org/10.1038/sj.bjp.0706405Mizuno, N., & Itoh, H. (2009). Functions and regulatory mechanisms of Gq-signaling pathways. Neuro-Signals, 17(1), 42-54. https://doi.org/10.1159/000186689Monsivais, P., Clark, B. A., Roth, A., & Häusser, M. (2005). Determinants of Action Potential Propagation in Cerebellar Purkinje Cell Axons. The Journal of Neuroscience, 25(2), 464-472. https://doi.org/10.1523/JNEUROSCI.3871-04.2005Müller-Oerlinghausen, B., Berghöfer, A., & Bauer, M. (2002). Bipolar disorder. Lancet (London, England), 359(9302), 241-247. https://doi.org/10.1016/S0140-6736(02)07450-0Netzeband, J. G., Parsons, K. L., Sweeney, D. D., & Gruol, D. L. (1997). Metabotropic glutamate receptor agonists alter neuronal excitability and Ca2+ levels via the phospholipase C transduction pathway in cultured Purkinje neurons. Journal of Neurophysiology, 78(1), 63-75. https://doi.org/10.1152/jn.1997.78.1.63Nolen, W. A., Licht, R. W., Young, A. H., Malhi, G. S., Tohen, M., Vieta, E., Kupka, R. W., Zarate, C., Nielsen, R. E., Baldessarini, R. J., & Severus, E. (2019). What is the optimal serum level for lithium in the maintenance treatment of bipolar disorder? A systematic review and recommendations from the ISBD/IGSLI Task Force on treatment with lithium. Bipolar Disorders, 21(5), 394-409. https://doi.org/10.1111/bdi.12805Nonaka, S., Hough, C. J., & Chuang, D. M. (1998). Chronic lithium treatment robustly protects neurons in the central nervous system against excitotoxicity by inhibiting N-methyl-D-aspartate receptor-mediated calcium influx. Proceedings of the National Academy of Sciences of the United States of America, 95(5), 2642-2647. https://doi.org/10.1073/pnas.95.5.2642Nunes, P., & Demaurex, N. (2010). The role of calcium signaling in phagocytosis. Journal of Leukocyte Biology, 88(1), 57-68. https://doi.org/10.1189/jlb.0110028Oldham, W. M., & Hamm, H. E. (2008). Heterotrimeric G protein activation by G-protein-coupled receptors. Nature Reviews. Molecular Cell Biology, 9(1), 60-71. https://doi.org/10.1038/nrm2299Partridge, L. D., & Thomas, R. C. (1974). Effect of intracellular lithium on snail neurones. Nature, 249(457), 578-580. https://doi.org/10.1038/249578a0Peinado, G., Osorno, T., Gomez, M. del P., & Nasi, E. (2015). Calcium activates the light-dependent conductance in melanopsin-expressing photoreceptors of amphioxus. Proceedings of the National Academy of Sciences, 112(25), 7845-7850. https://doi.org/10.1073/pnas.1420265112Perkel, D. J., Hestrin, S., Sah, P., & Nicoll, R. A. (1990). Excitatory synaptic currents in Purkinje cells. Proceedings. Biological Sciences, 241(1301), 116-121. https://doi.org/10.1098/rspb.1990.0074Phillips, M. L., & Kupfer, D. J. (2013). Bipolar disorder diagnosis: Challenges and future directions. The Lancet, 381(9878), 1663-1671. https://doi.org/10.1016/S0140-6736(13)60989-7Piochon, C., Irinopoulou, T., Brusciano, D., Bailly, Y., Mariani, J., & Levenes, C. (2007). NMDA receptor contribution to the climbing fiber response in the adult mouse Purkinje cell. The Journal of Neuroscience: The Official Journal of the Society for Neuroscience, 27(40), 10797-10809. https://doi.org/10.1523/JNEUROSCI.2422-07.2007Ploeger, E. J. (1974). The effects of lithium on excitable cell membranes. On the mechanism of inhibition of the sodium pump of non-myelinated nerve fibres of the rat. European Journal of Pharmacology, 25(3), 316-321. https://doi.org/10.1016/0014-2999(74)90261-1Pompili, M., Gonda, X., Serafini, G., Innamorati, M., Sher, L., Amore, M., Rihmer, Z., & Girardi, P. (2013). Epidemiology of suicide in bipolar disorders: A systematic review of the literature. Bipolar Disorders, 15(5), 457-490. https://doi.org/10.1111/bdi.12087Ransdell, J. L., & Nerbonne, J. M. (2018). Voltage-gated sodium currents in cerebellar Purkinje neurons: Functional and molecular diversity. Cellular and Molecular Life Sciences: CMLS, 75(19), 3495-3505. https://doi.org/10.1007/s00018-018-2868-yRenshaw, P. F., & Wicklund, S. (1988). In vivo measurement of lithium in humans by nuclear magnetic resonance spectroscopy. Biological Psychiatry, 23(5), 465-475. https://doi.org/10.1016/0006-3223(88)90018-2Reuveny, E., & Narahashi, T. (1993). Two types of high voltage-activated calcium channels in SH-SY5Y human neuroblastoma cells. Brain Research, 603(1), 64-73. https://doi.org/10.1016/0006-8993(93)91300-hRhee, S. G. (2001). Regulation of phosphoinositide-specific phospholipase C. Annual Review of Biochemistry, 70, 281-312. https://doi.org/10.1146/annurev.biochem.70.1.281Rossi, F., Buffo, A., & Strata, P. (2001). Regulation of intrinsic regenerative properties and axonal plasticity in cerebellar Purkinje cells. Restorative Neurology and Neuroscience, 19(1-2), 85-94.Roth, B. L. (2019). Molecular pharmacology of metabotropic receptors targeted by neuropsychiatric drugs. Nature Structural & Molecular Biology, 26(7), 535-544. https://doi.org/10.1038/s41594-019-0252-8Ryves, W. J., & Harwood, A. J. (2001). Lithium inhibits glycogen synthase kinase-3 by competition for magnesium. Biochemical and Biophysical Research Communications, 280(3), 720-725. https://doi.org/10.1006/bbrc.2000.4169Sánchez Triviño, C. A. (2019). Estudio fisiológico de los efectos del litio sobre la cascada de señalización mediada por la fosfolipasa C en modelos neuronales [Masters, Universidad Nacional de Colombia - Sede Bogotá]. http://bdigital.unal.edu.co/73555/Sassi, R. B., Nicoletti, M., Brambilla, P., Mallinger, A. G., Frank, E., Kupfer, D. J., Keshavan, M. S., & Soares, J. C. (2002). Increased gray matter volume in lithium-treated bipolar disorder patients. Neuroscience Letters, 329(2), 243-245. https://doi.org/10.1016/s0304-3940(02)00615-8Satoh, T., Ross, C. A., Villa, A., Supattapone, S., Pozzan, T., Snyder, S. H., & Meldolesi, J. (1990). The inositol 1,4,5,-trisphosphate receptor in cerebellar Purkinje cells: Quantitative immunogold labeling reveals concentration in an ER subcompartment. The Journal of Cell Biology, 111(2), 615-624. https://doi.org/10.1083/jcb.111.2.615Savitz, J. B., Price, J. L., & Drevets, W. C. (2014). Neuropathological and neuromorphometric abnormalities in bipolar disorder: View from the medial prefrontal cortical network. Neuroscience and Biobehavioral Reviews, 42, 132-147. https://doi.org/10.1016/j.neubiorev.2014.02.008Schilling, K., Dickinson, M. H., Connor, J. A., & Morgan, J. I. (1991). Electrical activity in cerebellar cultures determines Purkinje cell dendritic growth patterns. Neuron, 7(6), 891-902. https://doi.org/10.1016/0896-6273(91)90335-wSchmidt, H., Stiefel, K. M., Racay, P., Schwaller, B., & Eilers, J. (2003). Mutational analysis of dendritic Ca2+ kinetics in rodent Purkinje cells: Role of parvalbumin and calbindin D28k. The Journal of Physiology, 551(Pt 1), 13-32. https://doi.org/10.1113/jphysiol.2002.035824Shorter, E. (2009). The history of lithium therapy. Bipolar disorders, 11, 4-9. https://doi.org/10.1111/j.1399-5618.2009.00706.xSmith, F. E., Thelwall, P. E., Necus, J., Flowers, C. J., Blamire, A. M., & Cousins, D. A. (2018). 3D 7Li magnetic resonance imaging of brain lithium distribution in bipolar disorder. Molecular Psychiatry, 23(11), 2184-2191. https://doi.org/10.1038/s41380-018-0016-6Soboloff, J., Spassova, M., Hewavitharana, T., He, L. P., Luncsford, P., Xu, W., Venkatachalam, K., van Rossum, D., Patterson, R. L., & Gill, D. L. (2007). TRPC channels: Integrators of multiple cellular signals. Handbook of Experimental Pharmacology, 179, 575-591. https://doi.org/10.1007/978-3-540-34891-7_34Sossin, W. S., & Farah, C. A. (2009). Synaptic Plasticity: Diacylglycerol Signalling role. En L. R. Squire (Ed.), Encyclopedia of Neuroscience (pp. 747-755). Academic Press. https://doi.org/10.1016/B978-008045046-9.00820-2Sproule, B. A., Hardy, B. G., & Shulman, K. I. (2000). Differential pharmacokinetics of lithium in elderly patients. Drugs & Aging, 16(3), 165-177. https://doi.org/10.2165/00002512-200016030-00002Staub, C., Vranesic, I., & Knöpfel, T. (1992). Responses to Metabotropic Glutamate Receptor Activation in Cerebellar Purkinje Cells: Induction of an Inward Current. The European Journal of Neuroscience, 4(9), 832-839. https://doi.org/10.1111/j.1460-9568.1992.tb00193.xStout, J., Hozer, F., Coste, A., Mauconduit, F., Djebrani-Oussedik, N., Sarrazin, S., Poupon, J., Meyrel, M., Romanzetti, S., Etain, B., Rabrait-Lerman, C., Houenou, J., Bellivier, F., Duchesnay, E., & Boumezbeur, F. (2020). Accumulation of Lithium in the Hippocampus of Patients With Bipolar Disorder: A Lithium-7 Magnetic Resonance Imaging Study at 7 Tesla. Biological Psychiatry, 88(5), 426-433. https://doi.org/10.1016/j.biopsych.2020.02.1181Suh, B.-C., & Hille, B. (2008). PIP2 is a necessary cofactor for ion channel function: How and why? Annual review of biophysics, 37, 175-195. https://doi.org/10.1146/annurev.biophys.37.032807.125859Suzuki, N., Hajicek, N., & Kozasa, T. (2009). Regulation and physiological functions of G12/13-mediated signaling pathways. Neuro-Signals, 17(1), 55-70. https://doi.org/10.1159/000186690Syrovatkina, V., Alegre, K. O., Dey, R., & Huang, X.-Y. (2016). Regulation, Signaling, and Physiological Functions of G-Proteins. Journal of Molecular Biology, 428(19), 3850-3868. https://doi.org/10.1016/j.jmb.2016.08.002Tabata, T., Sawada, S., Araki, K., Bono, Y., Furuya, S., & Kano, M. (2000). A reliable method for culture of dissociated mouse cerebellar cells enriched for Purkinje neurons. Journal of Neuroscience Methods, 104(1), 45-53. https://doi.org/10.1016/s0165-0270(00)00323-xTanaka, J., Nakagawa, S., Kushiya, E., Yamasaki, M., Fukaya, M., Iwanaga, T., Simon, M. I., Sakimura, K., Kano, M., & Watanabe, M. (2000). Gq protein α subunits Gαq and Gα11 are localized at postsynaptic extra-junctional membrane of cerebellar Purkinje cells and hippocampal pyramidal cells. European Journal of Neuroscience, 12(3), 781-792. https://doi.org/10.1046/j.1460-9568.2000.00959.xTanaka, M. (2009). Dendrite formation of cerebellar Purkinje cells. Neurochemical Research, 34(12), 2078-2088. https://doi.org/10.1007/s11064-009-0073-yTempia, F., Alojado, M. E., Strata, P., & Knöpfel, T. (2001). Characterization of the mGluR(1)-mediated electrical and calcium signaling in Purkinje cells of mouse cerebellar slices. Journal of Neurophysiology, 86(3), 1389-1397. https://doi.org/10.1152/jn.2001.86.3.1389The Human Protein Atlas. (s. f.). Recuperado 8 de marzo de 2021, de https://www.proteinatlas.org/Thermo Fisher Scientific. (2020). Neurobiology protocol handbook. 136.Timmer, R. T., & Sands, J. M. (1999). Lithium intoxication. Journal of the American Society of Nephrology: JASN, 10(3), 666-674. https://doi.org/10.1681/ASN.V103666Tjaden, J., Pieczora, L., Wach, F., Theiss, C., & Theis, V. (2018). Cultivation of Purified Primary Purkinje Cells from Rat Cerebella. Cellular and Molecular Neurobiology, 38(7), 1399-1412. https://doi.org/10.1007/s10571-018-0606-5Tondo, L., Alda, M., Bauer, M., Bergink, V., Grof, P., Hajek, T., Lewitka, U., Licht, R. W., Manchia, M., Müller-Oerlinghausen, B., Nielsen, R. E., Selo, M., Simhandl, C., & Baldessarini, R. J. (2019). Clinical use of lithium salts: Guide for users and prescribers. International Journal of Bipolar Disorders, 7. https://doi.org/10.1186/s40345-019-0151-2Toselli, M., Masetto, S., Rossi, P., & Taglietti, V. (1991). Characterization of a Voltage-dependent Calcium Current in the Human Neuroblastoma Cell Line SH-SY5Y During Differentiation. The European Journal of Neuroscience, 3(6), 514-522. https://doi.org/10.1111/j.1460-9568.1991.tb00838.xToselli, M., Tosetti, P., & Taglietti, V. (1996). Functional changes in sodium conductances in the human neuroblastoma cell line SH-SY5Y during in vitro differentiation. Journal of Neurophysiology, 76(6), 3920-3927. https://doi.org/10.1152/jn.1996.76.6.3920Tosetti, P., Taglietti, V., & Toselli, M. (1998). Functional changes in potassium conductances of the human neuroblastoma cell line SH-SY5Y during in vitro differentiation. Journal of Neurophysiology, 79(2), 648-658. https://doi.org/10.1152/jn.1998.79.2.648Uhlén, M., Fagerberg, L., Hallström, B. M., Lindskog, C., Oksvold, P., Mardinoglu, A., Sivertsson, Å., Kampf, C., Sjöstedt, E., Asplund, A., Olsson, I., Edlund, K., Lundberg, E., Navani, S., Szigyarto, C. A.-K., Odeberg, J., Djureinovic, D., Takanen, J. O., Hober, S., … Pontén, F. (2015). Proteomics. Tissue-based map of the human proteome. Science (New York, N.Y.), 347(6220), 1260419. https://doi.org/10.1126/science.1260419Uhlen, M., Oksvold, P., Fagerberg, L., Lundberg, E., Jonasson, K., Forsberg, M., Zwahlen, M., Kampf, C., Wester, K., Hober, S., Wernerus, H., Björling, L., & Ponten, F. (2010). Towards a knowledge-based Human Protein Atlas. Nature Biotechnology, 28(12), 1248-1250. https://doi.org/10.1038/nbt1210-1248Vazquez, G., Wedel, B. J., Aziz, O., Trebak, M., & Putney, J. W. (2004). The mammalian TRPC cation channels. Biochimica Et Biophysica Acta, 1742(1-3), 21-36. https://doi.org/10.1016/j.bbamcr.2004.08.015Venkatachalam, K., Zheng, F., & Gill, D. L. (2003). Regulation of canonical transient receptor potential (TRPC) channel function by diacylglycerol and protein kinase C. The Journal of Biological Chemistry, 278(31), 29031-29040. https://doi.org/10.1074/jbc.M302751200Vetter, I., Mozar, C. A., Durek, T., Wingerd, J. S., Alewood, P. F., Christie, M. J., & Lewis, R. J. (2012). Characterisation of Na(v) types endogenously expressed in human SH-SY5Y neuroblastoma cells. Biochemical Pharmacology, 83(11), 1562-1571. https://doi.org/10.1016/j.bcp.2012.02.022Vieta, E., Berk, M., Schulze, T. G., Carvalho, A. F., Suppes, T., Calabrese, J. R., Gao, K., Miskowiak, K. W., & Grande, I. (2018). Bipolar disorders. Nature Reviews. Disease Primers, 4, 18008. https://doi.org/10.1038/nrdp.2018.8Vines, C. M. (2012). Phospholipase C. En Md. S. Islam (Ed.), Calcium Signaling (pp. 235-254). Springer Netherlands. https://doi.org/10.1007/978-94-007-2888-2_10Walton, P. D., Airey, J. A., Sutko, J. L., Beck, C. F., Mignery, G. A., Südhof, T. C., Deerinck, T. J., & Ellisman, M. H. (1991). Ryanodine and inositol trisphosphate receptors coexist in avian cerebellar Purkinje neurons. The Journal of Cell Biology, 113(5), 1145-1157. https://doi.org/10.1083/jcb.113.5.1145Wang, H. Y., & Friedman, E. (1999). Effects of lithium on receptor-mediated activation of G proteins in rat brain cortical membranes. Neuropharmacology, 38(3), 403-414. https://doi.org/10.1016/s0028-3908(98)00197-xWhitaker, M. (2006). Calcium at Fertilization and in Early Development. Physiological Reviews, 86(1), 25-88. https://doi.org/10.1152/physrev.00023.2005Womack, M. D., Walker, J. W., & Khodakhah, K. (2000). Impaired calcium release in cerebellar Purkinje neurons maintained in culture. The Journal of General Physiology, 115(3), 339-346. https://doi.org/10.1085/jgp.115.3.339Worley, P. F., Baraban, J. M., & Snyder, S. H. (1989). Inositol 1,4,5-trisphosphate receptor binding: Autoradiographic localization in rat brain. The Journal of Neuroscience: The Official Journal of the Society for Neuroscience, 9(1), 339-346.Yamakawa, Y., & Hirano, T. (1999). Contribution of mGluR1 to the basal activity of a mouse cerebellar Purkinje neuron. Neuroscience Letters, 277(2), 103-106. https://doi.org/10.1016/s0304-3940(99)00852-6Yuzaki, M., & Mikoshiba, K. (1992). Pharmacological and immunocytochemical characterization of metabotropic glutamate receptors in cultured Purkinje cells. Journal of Neuroscience, 12(11), 4253-4263. https://doi.org/10.1523/JNEUROSCI.12-11-04253.1992Zhang, C., Zhu, Q., & Hua, T. (2010). Aging of cerebellar Purkinje cells. 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