Aproximación comportamental y glutamatérgica de un modelo de roedor del trastorno del espectro autista por exposición prenatal a ácido valproico

ilustraciones, fotografías, graficas

Autores:: Moreno Avendaño, Johana Andrea

Tipo de recurso:

Fecha de publicación:: 2022

Institución:: Universidad Nacional de Colombia

Repositorio:: Universidad Nacional de Colombia

Idioma:: spa

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network_acronym_str	UNACIONAL2
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repository_id_str
dc.title.spa.fl_str_mv	Aproximación comportamental y glutamatérgica de un modelo de roedor del trastorno del espectro autista por exposición prenatal a ácido valproico
dc.title.translated.eng.fl_str_mv	Behavioral and glutamatergic approach of a rodent model of autism spectrum disorder exposed to valproic acid prenatal
title	Aproximación comportamental y glutamatérgica de un modelo de roedor del trastorno del espectro autista por exposición prenatal a ácido valproico
spellingShingle	Aproximación comportamental y glutamatérgica de un modelo de roedor del trastorno del espectro autista por exposición prenatal a ácido valproico 610 - Medicina y salud::616 - Enfermedades Trastorno del Espectro Autista Intercambio Materno-Fetal Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos Autism Spectrum Disorder Maternal-Fetal Exchange Drug-Related Side Effects and Adverse Reactions Autismo Acido valproico Modelo animal Deficit comportamental Glutamato NMDA VPA TEA Autism Valproic acid Animal Model Behavioral deficit
title_short	Aproximación comportamental y glutamatérgica de un modelo de roedor del trastorno del espectro autista por exposición prenatal a ácido valproico
title_full	Aproximación comportamental y glutamatérgica de un modelo de roedor del trastorno del espectro autista por exposición prenatal a ácido valproico
title_fullStr	Aproximación comportamental y glutamatérgica de un modelo de roedor del trastorno del espectro autista por exposición prenatal a ácido valproico
title_full_unstemmed	Aproximación comportamental y glutamatérgica de un modelo de roedor del trastorno del espectro autista por exposición prenatal a ácido valproico
title_sort	Aproximación comportamental y glutamatérgica de un modelo de roedor del trastorno del espectro autista por exposición prenatal a ácido valproico
dc.creator.fl_str_mv	Moreno Avendaño, Johana Andrea
dc.contributor.advisor.none.fl_str_mv	Dueñas Gómez, Zulma Janeth Cárdenas Parra, Luis Fernando
dc.contributor.author.none.fl_str_mv	Moreno Avendaño, Johana Andrea
dc.contributor.researchgroup.spa.fl_str_mv	Neurofisiologia Celular
dc.subject.ddc.spa.fl_str_mv	610 - Medicina y salud::616 - Enfermedades
topic	610 - Medicina y salud::616 - Enfermedades Trastorno del Espectro Autista Intercambio Materno-Fetal Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos Autism Spectrum Disorder Maternal-Fetal Exchange Drug-Related Side Effects and Adverse Reactions Autismo Acido valproico Modelo animal Deficit comportamental Glutamato NMDA VPA TEA Autism Valproic acid Animal Model Behavioral deficit
dc.subject.other.spa.fl_str_mv	Trastorno del Espectro Autista Intercambio Materno-Fetal Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos
dc.subject.other.eng.fl_str_mv	Autism Spectrum Disorder Maternal-Fetal Exchange Drug-Related Side Effects and Adverse Reactions
dc.subject.proposal.spa.fl_str_mv	Autismo Acido valproico Modelo animal Deficit comportamental
dc.subject.proposal.none.fl_str_mv	Glutamato NMDA VPA TEA
dc.subject.proposal.eng.fl_str_mv	Autism Valproic acid Animal Model Behavioral deficit
description	ilustraciones, fotografías, graficas
publishDate	2022
dc.date.accessioned.none.fl_str_mv	2022-09-05T13:47:27Z
dc.date.available.none.fl_str_mv	2022-09-05T13:47:27Z
dc.date.issued.none.fl_str_mv	2022-05
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/82248
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/82248 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.indexed.spa.fl_str_mv	RedCol LaReferencia
dc.relation.references.spa.fl_str_mv	Arndt, T. L., Stodgell, C. J., & Rodier, P. M. (2005). The teratology of autism. International Journal of Developmental Neuroscience, 23(2–3), 189–199. https://doi.org/10.1016/j.ijdevneu.2004.11.001 Baronio, D., Castro, K., Gonchoroski, T., de Melo, G., Nunes. GD, Bambini-Junior, V., Gottfried, C., & Riesgo, R. (2015). Effects of an H3R antagonist on the animal model of autism induced by prenatal exposure to valproic acid. PloS One, 10(1). https://doi.org/10.1371/JOURNAL.PONE.0116363 Bennett, G., Wlodarczyk, B., Calvin, J., Craig, J., & Finnell, R. (2000). Valproic acid induced alterations in growth and neurotrophic factor. Reprod Toxicol, 14, 1–11. Cheaha, D., Bumrungsri, S., Chatpun, S., & Kumarnsit, E. (2015). Characterization of in utero valproic acid mouse model of autism by local field potential in the hippocampus and the olfactory bulb. Neuroscience Research, 98, 28–34. https://doi.org/10.1016/j.neures.2015.04.006 Fujiki, R., Sato, A., Fujitani, M., & Yamashita, T. (2013). A proapoptotic effect of valproic acid on progenitors of embryonic stem cell-derived glutamatergic neurons. Cell Death and Disease, 4. https://doi.org/10.1038/cddis.2013.205 Gandhi, T., & Lee, C. C. (2020). Neural Mechanisms Underlying Repetitive Behaviors in Rodent Models of Autism Spectrum Disorders. Frontiers in Cellular Neuroscience, 14. https://doi.org/10.3389/FNCEL.2020.592710 Jensen, V., Rinholm, J. E., Johansen, T. J., Medin, T., Storm-Mathisen, J., Sagvolden, T., Hvalby, & Bergersen, L. H. (2009). N-methyl-d-aspartate receptor subunit dysfunction at hippocampal glutamatergic synapses in an animal model of attention-deficit/hyperactivity disorder. Neuroscience, 158(1), 353–364. https://doi.org/10.1016/j.neuroscience.2008.05.016 McFarlane, H., Kusek. GK, Yang, M., Phoenix, J., Bolivar, V., & Crawley, J. (2008). Autism-like behavioral phenotypes in BTBR T+tf/J mice. Genes, Brain, and Behavior, 7(2), 152–163. https://doi.org/10.1111/J.1601-183X.2007.00330.X Ruhela, R., Sarma, P., Soni, S., Prakash, A., & Medhi, B. (2017). Congenital malformation and autism spectrum disorder: Insight from a rat model of autism spectrum disorder. Indian Journal of Pharmacology, 49(3). https://doi.org/10.4103/ijp.IJP_183_17 Rinaldi, T., Kulangara, K., Antoniello, K., & Markram, H. (2007). Elevated NMDA receptor levels and enhanced postsynaptic long-term potentiation induced by prenatal exposure to valproic acid. Proceedings of the National Academy of Sciences, 104(33), 13501–13506. https://doi.org/10.1073/pnas.0704391104 Arndt, T. L., Stodgell, C. J., & Rodier, P. M. (2005). The teratology of autism. International Journal of Developmental Neuroscience, 23(2–3), 189–199. https://doi.org/10.1016/j.ijdevneu.2004.11.001 Artigas-Pallares, J., & Paula, I. (2012). El autismo 70 años después de Leo Kanner y Hans Asperger. Revista de La Asociación Española de Neuropsiquiatría, 32(115), 567–587. https://doi.org/10.4321/S021157352012000300008 Banerjee, A., Garcia-Oscos, F., Roychowdhury, S., Galindo, L., Hall, S., & Kilgard, M. (2013a). Impairment of cortical GABAergic synaptic transmission in an environmental rat model of autism. Int J Neuropsychopharmacol, 16, 1309–18. Banerjee, A., Garcia-Oscos, F., Roychowdhury, S., Galindo, L., Hall, S., & Kilgard, M. (2013b). Impairment of cortical GABAergic synaptic transmission in an environmental rat model of autism. Int J Neuropsychopharmacol, 16, 1309–18. Baronio, D., Castro, K., Gonchoroski, T., de Melo, G. M., Nunes, G. D. F., Bambini-Junior, V., Gottfried, C., & Riesgo, R. (2015). Effects of an H3R Antagonist on the Animal Model of Autism Induced by Prenatal Exposure to Valproic Acid. PLOS ONE, 10(1), e0116363. https://doi.org/10.1371/journal.pone.0116363 Baronio, D., Castro, K., Gonchoroski, T., de Melo, G., Nunes. GD, Bambini-Junior, V., Gottfried, C., & Riesgo, R. (2015). Effects of an H3R antagonist on the animal model of autism induced by prenatal exposure to valproic acid. PloS One, 10(1). https://doi.org/10.1371/JOURNAL.PONE.0116363 Belzung, C., Leman, S., Vourc’h, P., & Andres, C. (2005). Rodent models for autism: A critical review. Drug Discovery Today: Disease Models, 2(2), 93–101. https://doi.org/10.1016/j.ddmod.2005.05.004 Bennett, G., Wlodarczyk, B., Calvin, J., Craig, J., & Finnell, R. (2000). Valproic acid induced alterations in growth and neurotrophic factor. Reprod Toxicol, 14, 1–11. Burrows, E. L., Laskaris, L., Koyama, L., Churilov, L., Bornstein, J. C., Hill-yardin, E. L., & Hannan, A. J. (2015). A neuroligin-3 mutation implicated in autism causes abnormal aggression and increases repetitive behavior in mice. Molecular Autism, 6, 1–11. https://doi.org/10.1186/s13229-015-0055-7 Cheaha, D., Bumrungsri, S., Chatpun, S., & Kumarnsit, E. (2015). Characterization of in utero valproic acid mouse model of autism by local field potential in the hippocampus and the olfactory bulb. Neuroscience Research, 98, 28–34. https://doi.org/10.1016/j.neures.2015.04.006 Choudhury, P. R., Lahiri, S., & Rajamma, U. (2012). Glutamate mediated signaling in the pathophysiology of autism spectrum disorders. Pharmacology Biochemistry and Behavior, 100(4), 841–849. https://doi.org/10.1016/j.pbb.2011.06.023 Dufour-Rainfray, D., Vourc’h, P., Le Guisquet, A.-M., Garreau, L., Ternant, D., Bodard, S., Jaumain, E., Gulhan, Z., Belzung, C., Andres, C. R., Chalon, S., & Guilloteau, D. (2010). Behavior and serotonergic disorders in rats exposed prenatally to valproate: A model for autism. Neuroscience Letters, 470(1), 55–59. https://doi.org/10.1016/j.neulet.2009.12.054 Famitafreshi, H., & Karimian, M. (2018). Overview of the Recent Advances in Pathophysiology and Treatment for Autism. CNS & Neurological Disorders Drug Targets, 17(8), 590–594. https://doi.org/10.2174/1871527317666180706141654 Fatemi, S. H., Reutiman, T. J., Folsom, T. D., Rooney, R. J., Patel, D. H., & Thuras, P. D. (2010). mRNA and Protein levels for GABAA alpha 4, Alpha 5, Beta 1 and GABABR 1 receptors are altered in brains from subjects with autism. J. Autism Dev.Disord, 40, 743–750. https://doi.org/doi: 10.1007/s10803-0090924-z Favre, M. R., Barkat, T. R., Lamendola, D., Khazen, G., Markram, H., & Markram, K. (2013). General developmental health in the VPA-rat model of autism. Frontiers in Behavioral Neuroscience, 7, 88. https://doi.org/10.3389/fnbeh.2013.00088 Fujiki, R., Sato, A., Fujitani, M., & Yamashita, T. (2013). A proapoptotic effect of valproic acid on progenitors of embryonic stem cell-derived glutamatergic neurons. Cell Death and Disease, 4. https://doi.org/10.1038/cddis.2013.205 Fuller, L. C., Cornelius, S. K., Murphy, C. W., & Wiens, D. J. (2002). Neural crest cell motility in valproic acid. Reproductive Toxicology, 16(May), 825–839. Gandal, M. J., Edgar, J. C., Ehrlichman, R. S., Mehta, M., Roberts, T. P. L., & Siegel, S. J. (2010). Validating γ Oscillations and Delayed Auditory Responses as Translational Biomarkers of Autism. Biological Psychiatry, 68(12), 1100–1106. https://doi.org/10.1016/j.biopsych.2010.09.031 Gandhi, T., & Lee, C. C. (2020). Neural Mechanisms Underlying Repetitive Behaviors in Rodent Models of Autism Spectrum Disorders. Frontiers in Cellular Neuroscience, 14. https://doi.org/10.3389/FNCEL.2020.592710 Go, H. S., Seo, J. E., Kim, K. C., Han, S. M., Kim, P., Kang, Y. S., Han, S. H., Shin, C. Y., & Ko, K. H. (2011). Valproic acid inhibits neural progenitor cell death by activation of NF-κB signaling pathway and upregulation of Bcl-XL. J Biomed Sci, 18(1), 48. https://doi.org/1423-0127-18-48 [pii] 10.1186/14230127-18-48 Greer, P., Hanayama, R., Bloodgood, B., Mardinly, A., Lipton, D., Flavell, S., Kim, T., Griffith, E., Waldon, Z., & Maehr R, et al. (2010). The Angelman Syndrome protein Ube3A regulates synapse development by ubiquitinating arc. Cell, 140, 704–716. Grzadzinski, R., Huerta, M., & Lord, C. (2013). DSM-5 and autism spectrum disorders (ASDs): an opportunity for identifying ASD subtypes. Mol. Autism, 4. Harkness, J., & Ridgway, M. (1980). Chromodacryorrhea in laboratory rats (Rattus norvegicus): etiologic considerations. . Lab Anim Sci., 30(5), 841–844. Ingram, J. L., Peckham, S. M., Tisdale, B., & Rodier, P. M. (2000). Prenatal exposure of rats to valproic acid reproduces the cerebellar anomalies associated with autism. Neurotoxicology and Teratology, 22(3), 319–324. https://doi.org/10.1016/S0892-0362(99)00083-5 Jensen, V., Rinholm, J. E., Johansen, T. J., Medin, T., Storm-Mathisen, J., Sagvolden, T., Hvalby, & Bergersen, L. H. (2009). N-methyl-d-aspartate receptor subunit dysfunction at hippocampal glutamatergic synapses in an animal model of attention-deficit/hyperactivity disorder. Neuroscience, 158(1), 353–364. https://doi.org/10.1016/j.neuroscience.2008.05.016 Kim, D. G., Gonzales, E. L., Kim, S., Kim, Y., Adil, K. J., Jeon, S. J., Cho, K. S., Kwon, K. J., & Shin, and C. Y. (2019). Social Interaction Test in Home Cage as a Novel and Ethological Measure of Social Behavior in Mice. Experimental Neurobiology, 28(2), 247–260. https://doi.org/10.5607/EN.2019.28.2.247 Kim, J.-W., Seung, H., Kwon, K. J., Ko, M. J., Lee, E. J., Oh, H. A., Choi, C. S., Kim, K. C., Gonzales, E. L., You, J. S., Choi, D.-H., Lee, J., Han, S.-H., Yang, S. M., Cheong, J. H., Shin, C. Y., & Bahn, G. H. (2014). Subchronic Treatment of Donepezil Rescues Impaired Social, Hyperactive, and Stereotypic Behavior in Valproic Acid-Induced Animal Model of Autism. PLOS ONE, 9(8), e104927. https://doi.org/10.1371/JOURNAL.PONE.0104927 Kim, K. C., Kim, P., Go, H. S., Choi, C. S., Park, J. H., Kim, H. J., Jeon, S. J., Dela Pena, I. C., Han, S. H., Cheong, J. H., Ryu, J. H., & Shin, C. Y. (2013). Male-specific alteration in excitatory post-synaptic development and social interaction in pre-natal valproic acid exposure model of autism spectrum disorder. Journal of Neurochemistry, 124(6), 832–843. https://doi.org/10.1111/jnc.12147 Kim, K. C., Kim, P., Go, H. S., Choi, C. S., Park, J. H., Kim, H. J., Jeon, S. J., dela Pena, I. C., Han, S. H., Cheong, J. H., Ryu, J. H., & Shin, C. Y. (2013). Male-specific alteration in excitatory post-synaptic development and social interaction in pre-natal valproic acid exposure model of autism spectrum disorder. Journal of Neurochemistry, 124(6), 832–843. https://doi.org/10.1111/jnc.12147 Kim, K. C., Kim, P., Go, H. S., Choi, C. S., Park, J. H., Kim, H. J., Jeon, S. J., Pena, I. C. dela, Han, S.-H., Cheong, J. H., Ryu, J. H., & Shin, C. Y. (2013). Male-specific alteration in excitatory post-synaptic development and social interaction in pre-natal valproic acid exposure model of autism spectrum disorder. Journal of Neurochemistry, 124(6), 832–843. https://doi.org/10.1111/JNC.12147 Kumar, H., & Sharma, B. (2016). Memantine ameliorates autistic behavior, biochemistry & blood brain barrier impairments in rats. Brain Research Bulletin, 124, 27–39. https://doi.org/10.1016/J.BRAINRESBULL.2016.03.013 Lee, E.-J., Choi, S. Y., & Kim, E. (2015). NMDA receptor dysfunction in autism spectrum disorders. Current Opinion in Pharmacology, 20(JANUARY 2015), 8–13. https://doi.org/10.1016/j.coph.2014.10.007 Löscher, W. (1999). Valproate: a reappraisal of its pharmacodynamic properties and mechanisms of action. Progress in Neurobiology, 58(1), 31–59. https://doi.org/10.1016/S0301-0082(98)00075-6 Markram, K., & Foster, J. A. (2013). General developmental health in the VPA-rat model of autism. 7(July), 1–11. https://doi.org/10.3389/fnbeh.2013.00088 Markram, K., Rinaldi, T., Mendola, D. La, Sandi, C., & Markram, H. (2008). Abnormal Fear Conditioning and Amygdala Processing in an Animal Model of Autism. Neuropsychopharmacology, 33(4), 901–912. https://doi.org/10.1038/sj.npp.1301453 McFarlane, H., Kusek. GK, Yang, M., Phoenix, J., Bolivar, V., & Crawley, J. (2008). Autism-like behavioral phenotypes in BTBR T+tf/J mice. Genes, Brain, and Behavior, 7(2), 152–163. https://doi.org/10.1111/J.1601-183X.2007.00330.X Mehta, M. V., Gandal, M. J., & Siegel, S. J. (2011). mGluR5-Antagonist Mediated Reversal of Elevated Stereotyped, Repetitive Behaviors in the VPA Model of Autism. PLoS ONE, 6(10), e26077. https://doi.org/10.1371/journal.pone.0026077 Min de salud de Colombia. (2015). PROTOCOLO CLÍNICO PARA EL DIAGNÓSTICO, TRATAMIENTO Y RUTA DE ATENCIÓN INTEGRAL DE NIÑOS Y NIÑAS CON TRASTORNOS DEL ESPECTRO AUTISTA. Modi, M. E., & Young, L. J. (2012). The oxytocin system in drug discovery for autism: animal models and novel therapeutic strategies. Horm. Behav, 61, 340–350. https://doi.org/10.1016/j.yhbeh. 2011.12.010 Moore, S. J. (2000). A clinical study of 57 children with fetal anticonvulsant syndromes. Journal of Medical Genetics, 37(7), 489–497. https://doi.org/10.1136/jmg.37.7.489 Nazeer, A., & Ghaziuddin, M. (2012). Autism spectrum disorders: clinical features and diagnosis. Pediatr. Clin. North Am., 59(1), 19–25. Nimmo-Smith, V., Heuvelman, H., Dalman, C., Lundberg, M., Idring, S., Carpenter. P, Magnusson. C, & Rai. D. (2020). Anxiety Disorders in Adults with Autism Spectrum Disorder: A Population-Based Study. Palermo, M. T., & Curatolo, P. (2004). Pharmacologic treatment of autism. J. Child Neurol, 19, 155–164. Paradis, F.-H., & Hales, B. F. (2012). Exposure to Valproic Acid Inhibits Chondrogenesis and Osteogenesis in Mid-Organogenesis Mouse Limbs. https://doi.org/10.1093/toxsci/kfs292 Richler, J., Bishop, S., Kleinke. JR, & Lord, C. (2007). Restricted and repetitive behaviors in young children with autism spectrum disorders. Journal of Autism and Developmental Disorders, 37(1), 73–85. https://doi.org/10.1007/S10803-006-0332-6 Rinaldi. (2008). Hyper-connectivity and hyper-plasticity in the medial prefrontal cortex in the valproic acid animal model of autism. Frontiers in Neural Circuits, 2. https://doi.org/10.3389/neuro.04.004.2008 Rinaldi, T., Kulangara, K., Antoniello, K., & Markram, H. (2007). Elevated NMDA receptor levels and enhanced postsynaptic long-term potentiation induced by prenatal exposure to valproic acid. Proceedings of the National Academy of Sciences, 104(33), 13501–13506. https://doi.org/10.1073/pnas.0704391104 Rodier, P. M. (2002). Converging evidence for brain stem injury in autism. Development and Psychopathology, 14(03). https://doi.org/10.1017/S0954579402003085 Rodier, P. M., Ingram, J. L., Tisdale, B., Nelson, S., & Romano, J. (1996). Embryological Origin for Autism : Developmental Anomalies of the Cranial Nerve Motor Nuclei. The Journal of Comparative Neurology, 370, 2447–261. Ronesi, J., Collins, K., Hays, S., Tsai, N., Guo, W., & Birnbaum, S. (2012). Disrupted Homer scaffolds mediate abnormal mGluR5 function in a mouse model of fragile X syndrome. Nat Neurosci, 15, 431–40. Roullet, F. I., Lai, J. K. Y., & Foster, J. A. (2013). In utero exposure to valproic acid and autism — A current review of clinical and animal studies. Neurotoxicology and Teratology, 36, 47–56. https://doi.org/10.1016/j.ntt.2013.01.004 Ruhela, R., Sarma, P., Soni, S., Prakash, A., & Medhi, B. (2017). Congenital malformation and autism spectrum disorder: Insight from a rat model of autism spectrum disorder. Indian Journal of Pharmacology, 49(3). https://doi.org/10.4103/ijp.IJP_183_17 Sailer, L., Duclot, F., Wang, Z., & Kabbaj, M. (2019). Consequences of prenatal exposure to valproic acid in the socially monogamous prairie voles. Scientific Reports, 9(1). https://doi.org/10.1038/S41598-01939014-7 Schneider, T., & Przewłocki, R. (2005). Behavioral Alterations in Rats Prenatally Exposed to Valproic Acid: Animal Model of Autism. Neuropsychopharmacology, 30(1), 80–89. https://doi.org/10.1038/sj.npp.1300518 Schneider, T., Roman, A., Basta-Kaim, A., Kubera, M., Budziszewska, B., Schneider, K., & Przewłocki, R. (2008). Gender-specific behavioral and immunological alterations in an animal model of autism induced by prenatal exposure to valproic acid. Psychoneuroendocrinology, 33(6), 728–740. https://doi.org/10.1016/J.PSYNEUEN.2008.02.011 Schneider, T., Ziòłkowska, B., Gieryk, A., Tyminska, A., & Przewłocki, R. (2007). Prenatal exposure to valproic acid disturbs the enkephalinergic system functioning, basal hedonic tone, and emotional responses in an animal model of autism. Psychopharmacology, 193(4), 547–555. https://doi.org/10.1007/s00213-007-0795-y Sheng, M. & Kim, E. (2011). The postsynaptic organization of synapses. Cold Spring Harb. Perspect., 3(a005678). Silverman, J. L., Tolu, S. S., Barkan, C. L., & Crawley, J. N. (2010). Repetitive Self-Grooming Behavior in the BTBR Mouse Model of Autism is Blocked by the mGluR5 Antagonist MPEP. Neuropsychopharmacology, 35(4), 976. https://doi.org/10.1038/NPP.2009.201 Spooren, W., Lindemann, L., Ghosh, A., & Santarelli, L. (2012). Synapse dysfunction in autism : a molecular medicine approach to drug discovery in neurodevelopmental disorders. Trends in Pharmacological Sciences, 33(12), 669–684. https://doi.org/10.1016/j.tips.2012.09.004 Stromland, K., Nordin, V., Miller, M., Akerstrom, B., & Gillberg, C. (1994). Autism in thalidomide embryopathy: a population study. Developmental Medicine & Child Neurology, 36, 351–356. Tang, S., Terzic, B., Wang, I.-T. J., Sarmiento, N., Sizov, K., Cui, Y., Takano, H., Marsh, E. D., Zhou, Z., & Coulter, D. A. (2019). Altered NMDAR signaling underlies autistic-like features in mouse models of CDKL5 deficiency disorder. Nature Communications, 10(1). https://doi.org/10.1038/S41467-01910689-W Tashiro, Y., Oyabu, A., Imura, Y., Uchida, A., Narita, N., & Narita, M. (2011). Morphological abnormalities of embryonic cranial nerves after in utero exposure to valproic acid: implications for the pathogenesis of autism with multiple developmental anomalies. International Journal of Developmental Neuroscience, 29(4), 359–364. https://doi.org/10.1016/j.ijdevneu.2011.03.008 Vanderschuren, L. J. M. J., Achterberg, E. J. M., & Trezza, V. (2016). The neurobiology of social play and its rewarding value in rats. Neuroscience & Biobehavioral Reviews, 70. https://doi.org/10.1016/j.neubiorev.2016.07.025 Vasa, R., & Mazurek, M. (2015). An update on anxiety in youth with autism spectrum disorders. Current Opinion in Psychiatry, 28(2), 83–90. https://doi.org/10.1097/YCO.0000000000000133 Vorstman, J. A. S., Parr, J. R., Moreno-De-Luca, D., Anney, R. J. L., Nurnberger, J. I., & Hallmayer, J. F. (2017). Autism genetics: opportunities and challenges for clinical translation. Nature Reviews. Genetics, 18(6), 362–376. https://doi.org/10.1038/NRG.2017.4 Whitehouse, C. M., & Lewis, M. H. (2015). Repetitive Behavior in Neurodevelopmental Disorders: Clinical and Translational Findings. The Behavior Analyst, 38(2), 163. https://doi.org/10.1007/S40614-0150029-2 Williams, P., & Hersh, J. (1997). A male with fetal valproate syndrome and autism. Developmental Medicine & Child Neurology, 39, 632–634. Wu, L. J., Toyoda, H., Zhao, M. G., Lee, Y. S., Tang, J., Ko, S. W., Yong, H. J., Shum, F. W. F., Zerbinatti, C. v., Bu, G., Wei, F., Xu, T. le, Muglia, L. J., Chen, Z. F., Auberson, Y. P., Kaang, B. K., & Zhuo, M. (2005). Upregulation of forebrain NMDA NR2B receptors contributes to behavioral sensitization after inflammation. Journal of Neuroscience, 25(48), 11107–11116. https://doi.org/10.1523/JNEUROSCI.1678-05.2005 Xu, J. Y., Xia, Q. Q., & Xia, J. (2012). A review on the current neuroligin mouse models. Sheng Li Xue Bao, 64, 550–562. Yang, E. J., Ahn, S., Lee, K., Mahmood, U., & Kim, H. S. (2016). Early behavioral abnormalities and perinatal alterations of PTEN/AKT pathway in valproic acid autism model mice. PLoS ONE, 11(4). https://doi.org/10.1371/journal.pone.0153298 Yang, M., Silverman, J. L., & Crawley, J. N. (2011). Automated three-chambered social approach task for mice. Current Protocols in Neuroscience, SUPPL. 56. https://doi.org/10.1002/0471142301.NS0826S56 Yu, Y., Chaulagain, A., Pedersen, S., Lydersen, S., Leventhal, B., Szatmari, P., Aleksic, B., Ozaki, N., & Skokauskas, N. (2020). Pharmacotherapy of restricted/repetitive behavior in autism spectrum disorder:a systematic review and meta-analysis. BMC Psychiatry, 20(1). https://doi.org/10.1186/S12888-020-2477-9 Zoghbi, H., & Bear, M. (2012). Synaptic Dysfunction in Neurodevelopmental Intellectual Disabilities. Cold Spring Harb. Perspect. Biol., 4(3), 1–22. https://doi.org/10.1101/cshperspect.a009886
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dc.rights.license.spa.fl_str_mv	Atribución-SinDerivadas 4.0 Internacional
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dc.format.extent.spa.fl_str_mv	123 páginas
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dc.publisher.spa.fl_str_mv	Universidad Nacional de Colombia
dc.publisher.program.spa.fl_str_mv	Bogotá - Medicina - Maestría en Neurociencias
dc.publisher.faculty.spa.fl_str_mv	Facultad de Medicina
dc.publisher.place.spa.fl_str_mv	Bogotá, Colombia
dc.publisher.branch.spa.fl_str_mv	Universidad Nacional de Colombia - Sede Bogotá
institution	Universidad Nacional de Colombia
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spelling	Atribución-SinDerivadas 4.0 Internacionalhttp://creativecommons.org/licenses/by-nd/4.0/info:eu-repo/semantics/openAccesshttp://purl.org/coar/access_right/c_abf2Dueñas Gómez, Zulma Janeth12c9a5d786762f195e89a27a45656805600Cárdenas Parra, Luis Fernando0d0dde21cd90ef044e6cac042bde5bc1Moreno Avendaño, Johana Andreac5d304c0c2bea555ea0a97db9d391d7cNeurofisiologia Celular2022-09-05T13:47:27Z2022-09-05T13:47:27Z2022-05https://repositorio.unal.edu.co/handle/unal/82248Universidad Nacional de ColombiaRepositorio Institucional Universidad Nacional de Colombiahttps://repositorio.unal.edu.co/ilustraciones, fotografías, graficasEl trastorno del espectro autista (TEA) es considerado un desorden en el neurodesarrollo caracterizado por déficit en la interacción social, la comunicación y presencia de comportamientos repetitivos y estereotipados. Se estima que aproximadamente un 16 % de la población menor de 15 años en Colombia padece algún tipo de trastorno del desarrollo, entre ellos los TEA. Colombia no cuenta con cifras oficiales que establezcan la prevalencia en el país de este trastorno. Estudios post-mortem y de imagenología diagnóstica se han aproximado a la neurobiología subyacente del TEA, sin embargo, los modelos animales permiten la exploración en detalle y en un entorno controlado de los mediadores neuroanatómicos, neurofisiológicos y moleculares, relacionados con el fenotipo del trastorno. La evidencia sugiere que los factores ambientales y las interacciones genético-ambientales contribuyen a la etiología del autismo, por ejemplo, la exposición prenatal a ácido Valpróico (por sus siglas en inglés: VPA), se asocia con una alta incidencia de autismo en los nacidos; de hecho, la embriogénesis temprana como periodo crítico para el desarrollo de trastornos del neurodesarrollo sustenta el desarrollo de biomodelos que emulan la complejidad fenotípica de la enfermedad. Teniendo en cuenta el potencial uso del modelo inducido por exposición prenatal al VPA para dilucidar aspectos biológicos y conductuales de la enfermedad en humanos, esta investigación pretendió describir los patrones morfológicos, comportamentales y moleculares de las crías de ratas hembra Wistar tratadas con una única dosis de 500 mg/Kg de VPA en el día 12.5 de gestación en comparación con controles expuestos a solución salina. Nuestros resultados evidencian una alta tasa de reabsorción fetal de las hembras tratadas, sin embargo, los embriones expuestos a VPA que sobrevivieron mostraron cambios neuroanatómicos, morfológicos y alteraciones comportamentales significativas respecto al grupo control. Se halló aumento en el número de nacidos con malformaciones físicas, defectos en la formación falanges, longitud y forma de la cola y casos esporádicos de cromodacriorrea, mientras que las pruebas comportamentales revelan alteraciones en la sociabilidad y repetitividad, comportamientos típicos del fenotipo autista humano. Los resultados de esta investigación sustentan el uso experimental del biomodelo de autismo por exposición prenatal al VPA, demuestran la validez aparente y de constructo del modelo y su potencial utilidad para el desarrollo de futuras líneas de investigación que profundicen aspectos clave en la compresión de la neurobiología del TEA y el hallazgo de blancos terapéuticos para el tratamiento de la enfermedad. (Texto tomado de la fuente)Autism Spectrum Disorder (ASD) is considered a neurodevelopmental disorder characterized by deficits in social interaction, communication, and the presence of repetitive and stereotyped behaviors. It is estimated that approximately 16% of the population under 15 years of age in Colombia will suffer from some type of developmental disorder, including ASD. Colombia does not have official figures that established the prevalence of this disorder in the country. On the other hand, post-mortem and diagnostic imaging studies have come closer to the underlying neurobiology of ASD, however, animal models allow the exploration in detail and in a controlled environment of the neuroanatomical, neurophysiological, and molecular mediators related to the phenotype of the disorder. Evidence suggests that environmental factors and gene-environment interactions contribute to the etiology of autism, for example, prenatal exposure to valproic acid (VPA) is associated with a high incidence of autism in newborns; in fact, early embryogenesis as a critical period for the development of neurodevelopmental disorders supports the development of biomodels that emulate the phenotypic complexity of the disease. Considering the potential use of the model induced by prenatal exposure to VPA to elucidate biological and behavioral factors of the disease in humans, this research aimed to describe the morphological, behavioral and molecular patterns of the offspring of female Wistar rats treated with a single dose of 500 mg/Kg VPA on day 12.5 of gestation compared to controls exposed to saline. Our results show a high rate of fetal resorption of the treated females, however, the embryos exposed to VPA that survived showed significant neuroanatomical, morphological, and behavioral changes compared to the control group. An increase in the number of babies born with physical malformations, defects in phalangeal formation, tail length and shape, and sporadic cases of chromodacryorrhea were found, while behavioral tests revealed alterations in sociability and repetitiveness, typical behaviors of the human autistic phenotype. The results of this research support the experimental use of the biomodel of autism due to prenatal exposure to VPA, demonstrate the apparent and construct validity of the model and its potential usefulness for the development of future lines of research that deepen key aspects in the understanding of neurobiology of ASD and the finding of therapeutic targets for the treatment of the disease.MaestríaMagíster en Neurociencias123 páginasapplication/pdfspaUniversidad Nacional de ColombiaBogotá - Medicina - Maestría en NeurocienciasFacultad de MedicinaBogotá, ColombiaUniversidad Nacional de Colombia - Sede Bogotá610 - Medicina y salud::616 - EnfermedadesTrastorno del Espectro AutistaIntercambio Materno-FetalEfectos Colaterales y Reacciones Adversas Relacionados con MedicamentosAutism Spectrum DisorderMaternal-Fetal ExchangeDrug-Related Side Effects and Adverse ReactionsAutismoAcido valproicoModelo animalDeficit comportamentalGlutamatoNMDAVPATEAAutismValproic acidAnimal ModelBehavioral deficitAproximación comportamental y glutamatérgica de un modelo de roedor del trastorno del espectro autista por exposición prenatal a ácido valproicoBehavioral and glutamatergic approach of a rodent model of autism spectrum disorder exposed to valproic acid prenatalTrabajo de grado - Maestríainfo:eu-repo/semantics/masterThesisinfo:eu-repo/semantics/acceptedVersionTexthttp://purl.org/redcol/resource_type/TMRedColLaReferenciaArndt, T. L., Stodgell, C. J., & Rodier, P. M. (2005). The teratology of autism. International Journal of Developmental Neuroscience, 23(2–3), 189–199. https://doi.org/10.1016/j.ijdevneu.2004.11.001Baronio, D., Castro, K., Gonchoroski, T., de Melo, G., Nunes. GD, Bambini-Junior, V., Gottfried, C., & Riesgo, R. (2015). Effects of an H3R antagonist on the animal model of autism induced by prenatal exposure to valproic acid. PloS One, 10(1). https://doi.org/10.1371/JOURNAL.PONE.0116363Bennett, G., Wlodarczyk, B., Calvin, J., Craig, J., & Finnell, R. (2000). Valproic acid induced alterations in growth and neurotrophic factor. Reprod Toxicol, 14, 1–11.Cheaha, D., Bumrungsri, S., Chatpun, S., & Kumarnsit, E. (2015). Characterization of in utero valproic acid mouse model of autism by local field potential in the hippocampus and the olfactory bulb. Neuroscience Research, 98, 28–34. https://doi.org/10.1016/j.neures.2015.04.006Fujiki, R., Sato, A., Fujitani, M., & Yamashita, T. (2013). A proapoptotic effect of valproic acid on progenitors of embryonic stem cell-derived glutamatergic neurons. Cell Death and Disease, 4. https://doi.org/10.1038/cddis.2013.205Gandhi, T., & Lee, C. C. (2020). Neural Mechanisms Underlying Repetitive Behaviors in Rodent Models of Autism Spectrum Disorders. Frontiers in Cellular Neuroscience, 14. https://doi.org/10.3389/FNCEL.2020.592710Jensen, V., Rinholm, J. E., Johansen, T. J., Medin, T., Storm-Mathisen, J., Sagvolden, T., Hvalby, & Bergersen, L. H. (2009). N-methyl-d-aspartate receptor subunit dysfunction at hippocampal glutamatergic synapses in an animal model of attention-deficit/hyperactivity disorder. Neuroscience, 158(1), 353–364. https://doi.org/10.1016/j.neuroscience.2008.05.016McFarlane, H., Kusek. GK, Yang, M., Phoenix, J., Bolivar, V., & Crawley, J. (2008). Autism-like behavioral phenotypes in BTBR T+tf/J mice. Genes, Brain, and Behavior, 7(2), 152–163. https://doi.org/10.1111/J.1601-183X.2007.00330.XRuhela, R., Sarma, P., Soni, S., Prakash, A., & Medhi, B. (2017). Congenital malformation and autism spectrum disorder: Insight from a rat model of autism spectrum disorder. Indian Journal of Pharmacology, 49(3). https://doi.org/10.4103/ijp.IJP_183_17Rinaldi, T., Kulangara, K., Antoniello, K., & Markram, H. (2007). Elevated NMDA receptor levels and enhanced postsynaptic long-term potentiation induced by prenatal exposure to valproic acid. Proceedings of the National Academy of Sciences, 104(33), 13501–13506. https://doi.org/10.1073/pnas.0704391104Arndt, T. L., Stodgell, C. J., & Rodier, P. M. (2005). The teratology of autism. International Journal of Developmental Neuroscience, 23(2–3), 189–199. https://doi.org/10.1016/j.ijdevneu.2004.11.001Artigas-Pallares, J., & Paula, I. (2012). El autismo 70 años después de Leo Kanner y Hans Asperger. Revista de La Asociación Española de Neuropsiquiatría, 32(115), 567–587. https://doi.org/10.4321/S021157352012000300008Banerjee, A., Garcia-Oscos, F., Roychowdhury, S., Galindo, L., Hall, S., & Kilgard, M. (2013a). Impairment of cortical GABAergic synaptic transmission in an environmental rat model of autism. Int J Neuropsychopharmacol, 16, 1309–18.Banerjee, A., Garcia-Oscos, F., Roychowdhury, S., Galindo, L., Hall, S., & Kilgard, M. (2013b). Impairment of cortical GABAergic synaptic transmission in an environmental rat model of autism. Int J Neuropsychopharmacol, 16, 1309–18.Baronio, D., Castro, K., Gonchoroski, T., de Melo, G. M., Nunes, G. D. F., Bambini-Junior, V., Gottfried, C., & Riesgo, R. (2015). Effects of an H3R Antagonist on the Animal Model of Autism Induced by Prenatal Exposure to Valproic Acid. PLOS ONE, 10(1), e0116363. https://doi.org/10.1371/journal.pone.0116363Baronio, D., Castro, K., Gonchoroski, T., de Melo, G., Nunes. GD, Bambini-Junior, V., Gottfried, C., & Riesgo, R. (2015). Effects of an H3R antagonist on the animal model of autism induced by prenatal exposure to valproic acid. PloS One, 10(1). https://doi.org/10.1371/JOURNAL.PONE.0116363Belzung, C., Leman, S., Vourc’h, P., & Andres, C. (2005). Rodent models for autism: A critical review. Drug Discovery Today: Disease Models, 2(2), 93–101. https://doi.org/10.1016/j.ddmod.2005.05.004Bennett, G., Wlodarczyk, B., Calvin, J., Craig, J., & Finnell, R. (2000). Valproic acid induced alterations in growth and neurotrophic factor. Reprod Toxicol, 14, 1–11.Burrows, E. L., Laskaris, L., Koyama, L., Churilov, L., Bornstein, J. C., Hill-yardin, E. L., & Hannan, A. J. (2015). A neuroligin-3 mutation implicated in autism causes abnormal aggression and increases repetitive behavior in mice. Molecular Autism, 6, 1–11. https://doi.org/10.1186/s13229-015-0055-7Cheaha, D., Bumrungsri, S., Chatpun, S., & Kumarnsit, E. (2015). Characterization of in utero valproic acid mouse model of autism by local field potential in the hippocampus and the olfactory bulb. Neuroscience Research, 98, 28–34. https://doi.org/10.1016/j.neures.2015.04.006Choudhury, P. R., Lahiri, S., & Rajamma, U. (2012). Glutamate mediated signaling in the pathophysiology of autism spectrum disorders. Pharmacology Biochemistry and Behavior, 100(4), 841–849. https://doi.org/10.1016/j.pbb.2011.06.023Dufour-Rainfray, D., Vourc’h, P., Le Guisquet, A.-M., Garreau, L., Ternant, D., Bodard, S., Jaumain, E., Gulhan, Z., Belzung, C., Andres, C. R., Chalon, S., & Guilloteau, D. (2010). Behavior and serotonergic disorders in rats exposed prenatally to valproate: A model for autism. Neuroscience Letters, 470(1), 55–59. https://doi.org/10.1016/j.neulet.2009.12.054Famitafreshi, H., & Karimian, M. (2018). Overview of the Recent Advances in Pathophysiology and Treatment for Autism. CNS & Neurological Disorders Drug Targets, 17(8), 590–594. https://doi.org/10.2174/1871527317666180706141654Fatemi, S. H., Reutiman, T. J., Folsom, T. D., Rooney, R. J., Patel, D. H., & Thuras, P. D. (2010). mRNA and Protein levels for GABAA alpha 4, Alpha 5, Beta 1 and GABABR 1 receptors are altered in brains from subjects with autism. J. Autism Dev.Disord, 40, 743–750. https://doi.org/doi: 10.1007/s10803-0090924-zFavre, M. R., Barkat, T. R., Lamendola, D., Khazen, G., Markram, H., & Markram, K. (2013). General developmental health in the VPA-rat model of autism. Frontiers in Behavioral Neuroscience, 7, 88. https://doi.org/10.3389/fnbeh.2013.00088Fujiki, R., Sato, A., Fujitani, M., & Yamashita, T. (2013). A proapoptotic effect of valproic acid on progenitors of embryonic stem cell-derived glutamatergic neurons. Cell Death and Disease, 4. https://doi.org/10.1038/cddis.2013.205Fuller, L. C., Cornelius, S. K., Murphy, C. W., & Wiens, D. J. (2002). Neural crest cell motility in valproic acid. Reproductive Toxicology, 16(May), 825–839.Gandal, M. J., Edgar, J. C., Ehrlichman, R. S., Mehta, M., Roberts, T. P. L., & Siegel, S. J. (2010). Validating γ Oscillations and Delayed Auditory Responses as Translational Biomarkers of Autism. Biological Psychiatry, 68(12), 1100–1106. https://doi.org/10.1016/j.biopsych.2010.09.031Gandhi, T., & Lee, C. C. (2020). Neural Mechanisms Underlying Repetitive Behaviors in Rodent Models of Autism Spectrum Disorders. Frontiers in Cellular Neuroscience, 14. https://doi.org/10.3389/FNCEL.2020.592710Go, H. S., Seo, J. E., Kim, K. C., Han, S. M., Kim, P., Kang, Y. S., Han, S. H., Shin, C. Y., & Ko, K. H. (2011). Valproic acid inhibits neural progenitor cell death by activation of NF-κB signaling pathway and upregulation of Bcl-XL. J Biomed Sci, 18(1), 48. https://doi.org/1423-0127-18-48 [pii] 10.1186/14230127-18-48Greer, P., Hanayama, R., Bloodgood, B., Mardinly, A., Lipton, D., Flavell, S., Kim, T., Griffith, E., Waldon, Z., & Maehr R, et al. (2010). The Angelman Syndrome protein Ube3A regulates synapse development by ubiquitinating arc. Cell, 140, 704–716.Grzadzinski, R., Huerta, M., & Lord, C. (2013). DSM-5 and autism spectrum disorders (ASDs): an opportunity for identifying ASD subtypes. Mol. Autism, 4.Harkness, J., & Ridgway, M. (1980). Chromodacryorrhea in laboratory rats (Rattus norvegicus): etiologic considerations. . Lab Anim Sci., 30(5), 841–844.Ingram, J. L., Peckham, S. M., Tisdale, B., & Rodier, P. M. (2000). Prenatal exposure of rats to valproic acid reproduces the cerebellar anomalies associated with autism. Neurotoxicology and Teratology, 22(3), 319–324. https://doi.org/10.1016/S0892-0362(99)00083-5Jensen, V., Rinholm, J. E., Johansen, T. J., Medin, T., Storm-Mathisen, J., Sagvolden, T., Hvalby, & Bergersen, L. H. (2009). N-methyl-d-aspartate receptor subunit dysfunction at hippocampal glutamatergic synapses in an animal model of attention-deficit/hyperactivity disorder. Neuroscience, 158(1), 353–364. https://doi.org/10.1016/j.neuroscience.2008.05.016Kim, D. G., Gonzales, E. L., Kim, S., Kim, Y., Adil, K. J., Jeon, S. J., Cho, K. S., Kwon, K. J., & Shin, and C. Y. (2019). Social Interaction Test in Home Cage as a Novel and Ethological Measure of Social Behavior in Mice. Experimental Neurobiology, 28(2), 247–260. https://doi.org/10.5607/EN.2019.28.2.247Kim, J.-W., Seung, H., Kwon, K. J., Ko, M. J., Lee, E. J., Oh, H. A., Choi, C. S., Kim, K. C., Gonzales, E. L., You, J. S., Choi, D.-H., Lee, J., Han, S.-H., Yang, S. M., Cheong, J. H., Shin, C. Y., & Bahn, G. H. (2014). Subchronic Treatment of Donepezil Rescues Impaired Social, Hyperactive, and Stereotypic Behavior in Valproic Acid-Induced Animal Model of Autism. PLOS ONE, 9(8), e104927. https://doi.org/10.1371/JOURNAL.PONE.0104927Kim, K. C., Kim, P., Go, H. S., Choi, C. S., Park, J. H., Kim, H. J., Jeon, S. J., Dela Pena, I. C., Han, S. H., Cheong, J. H., Ryu, J. H., & Shin, C. Y. (2013). Male-specific alteration in excitatory post-synaptic development and social interaction in pre-natal valproic acid exposure model of autism spectrum disorder. Journal of Neurochemistry, 124(6), 832–843. https://doi.org/10.1111/jnc.12147Kim, K. C., Kim, P., Go, H. S., Choi, C. S., Park, J. H., Kim, H. J., Jeon, S. J., dela Pena, I. C., Han, S. H., Cheong, J. H., Ryu, J. H., & Shin, C. Y. (2013). Male-specific alteration in excitatory post-synaptic development and social interaction in pre-natal valproic acid exposure model of autism spectrum disorder. Journal of Neurochemistry, 124(6), 832–843. https://doi.org/10.1111/jnc.12147Kim, K. C., Kim, P., Go, H. S., Choi, C. S., Park, J. H., Kim, H. J., Jeon, S. J., Pena, I. C. dela, Han, S.-H., Cheong, J. H., Ryu, J. H., & Shin, C. Y. (2013). Male-specific alteration in excitatory post-synaptic development and social interaction in pre-natal valproic acid exposure model of autism spectrum disorder. Journal of Neurochemistry, 124(6), 832–843. https://doi.org/10.1111/JNC.12147Kumar, H., & Sharma, B. (2016). Memantine ameliorates autistic behavior, biochemistry & blood brain barrier impairments in rats. Brain Research Bulletin, 124, 27–39. https://doi.org/10.1016/J.BRAINRESBULL.2016.03.013Lee, E.-J., Choi, S. Y., & Kim, E. (2015). NMDA receptor dysfunction in autism spectrum disorders. Current Opinion in Pharmacology, 20(JANUARY 2015), 8–13. https://doi.org/10.1016/j.coph.2014.10.007Löscher, W. (1999). Valproate: a reappraisal of its pharmacodynamic properties and mechanisms of action. Progress in Neurobiology, 58(1), 31–59. https://doi.org/10.1016/S0301-0082(98)00075-6Markram, K., & Foster, J. A. (2013). General developmental health in the VPA-rat model of autism. 7(July), 1–11. https://doi.org/10.3389/fnbeh.2013.00088Markram, K., Rinaldi, T., Mendola, D. La, Sandi, C., & Markram, H. (2008). Abnormal Fear Conditioning and Amygdala Processing in an Animal Model of Autism. Neuropsychopharmacology, 33(4), 901–912. https://doi.org/10.1038/sj.npp.1301453McFarlane, H., Kusek. GK, Yang, M., Phoenix, J., Bolivar, V., & Crawley, J. (2008). Autism-like behavioral phenotypes in BTBR T+tf/J mice. Genes, Brain, and Behavior, 7(2), 152–163. https://doi.org/10.1111/J.1601-183X.2007.00330.XMehta, M. V., Gandal, M. J., & Siegel, S. J. (2011). mGluR5-Antagonist Mediated Reversal of Elevated Stereotyped, Repetitive Behaviors in the VPA Model of Autism. PLoS ONE, 6(10), e26077. https://doi.org/10.1371/journal.pone.0026077Min de salud de Colombia. (2015). PROTOCOLO CLÍNICO PARA EL DIAGNÓSTICO, TRATAMIENTO Y RUTA DE ATENCIÓN INTEGRAL DE NIÑOS Y NIÑAS CON TRASTORNOS DEL ESPECTRO AUTISTA.Modi, M. E., & Young, L. J. (2012). The oxytocin system in drug discovery for autism: animal models and novel therapeutic strategies. Horm. Behav, 61, 340–350. https://doi.org/10.1016/j.yhbeh. 2011.12.010Moore, S. J. (2000). A clinical study of 57 children with fetal anticonvulsant syndromes. Journal of Medical Genetics, 37(7), 489–497. https://doi.org/10.1136/jmg.37.7.489Nazeer, A., & Ghaziuddin, M. (2012). Autism spectrum disorders: clinical features and diagnosis. Pediatr. Clin. North Am., 59(1), 19–25.Nimmo-Smith, V., Heuvelman, H., Dalman, C., Lundberg, M., Idring, S., Carpenter. P, Magnusson. C, & Rai. D. (2020). Anxiety Disorders in Adults with Autism Spectrum Disorder: A Population-Based Study.Palermo, M. T., & Curatolo, P. (2004). Pharmacologic treatment of autism. J. Child Neurol, 19, 155–164.Paradis, F.-H., & Hales, B. F. (2012). Exposure to Valproic Acid Inhibits Chondrogenesis and Osteogenesis in Mid-Organogenesis Mouse Limbs. https://doi.org/10.1093/toxsci/kfs292Richler, J., Bishop, S., Kleinke. JR, & Lord, C. (2007). Restricted and repetitive behaviors in young children with autism spectrum disorders. Journal of Autism and Developmental Disorders, 37(1), 73–85. https://doi.org/10.1007/S10803-006-0332-6Rinaldi. (2008). Hyper-connectivity and hyper-plasticity in the medial prefrontal cortex in the valproic acid animal model of autism. Frontiers in Neural Circuits, 2. https://doi.org/10.3389/neuro.04.004.2008Rinaldi, T., Kulangara, K., Antoniello, K., & Markram, H. (2007). Elevated NMDA receptor levels and enhanced postsynaptic long-term potentiation induced by prenatal exposure to valproic acid. Proceedings of the National Academy of Sciences, 104(33), 13501–13506. https://doi.org/10.1073/pnas.0704391104Rodier, P. M. (2002). Converging evidence for brain stem injury in autism. Development and Psychopathology, 14(03). https://doi.org/10.1017/S0954579402003085Rodier, P. M., Ingram, J. L., Tisdale, B., Nelson, S., & Romano, J. (1996). Embryological Origin for Autism : Developmental Anomalies of the Cranial Nerve Motor Nuclei. The Journal of Comparative Neurology, 370, 2447–261.Ronesi, J., Collins, K., Hays, S., Tsai, N., Guo, W., & Birnbaum, S. (2012). Disrupted Homer scaffolds mediate abnormal mGluR5 function in a mouse model of fragile X syndrome. Nat Neurosci, 15, 431–40.Roullet, F. I., Lai, J. K. Y., & Foster, J. A. (2013). In utero exposure to valproic acid and autism — A current review of clinical and animal studies. Neurotoxicology and Teratology, 36, 47–56. https://doi.org/10.1016/j.ntt.2013.01.004Ruhela, R., Sarma, P., Soni, S., Prakash, A., & Medhi, B. (2017). Congenital malformation and autism spectrum disorder: Insight from a rat model of autism spectrum disorder. Indian Journal of Pharmacology, 49(3). https://doi.org/10.4103/ijp.IJP_183_17Sailer, L., Duclot, F., Wang, Z., & Kabbaj, M. (2019). Consequences of prenatal exposure to valproic acid in the socially monogamous prairie voles. Scientific Reports, 9(1). https://doi.org/10.1038/S41598-01939014-7Schneider, T., & Przewłocki, R. (2005). Behavioral Alterations in Rats Prenatally Exposed to Valproic Acid: Animal Model of Autism. Neuropsychopharmacology, 30(1), 80–89. https://doi.org/10.1038/sj.npp.1300518Schneider, T., Roman, A., Basta-Kaim, A., Kubera, M., Budziszewska, B., Schneider, K., & Przewłocki, R. (2008). Gender-specific behavioral and immunological alterations in an animal model of autism induced by prenatal exposure to valproic acid. Psychoneuroendocrinology, 33(6), 728–740. https://doi.org/10.1016/J.PSYNEUEN.2008.02.011Schneider, T., Ziòłkowska, B., Gieryk, A., Tyminska, A., & Przewłocki, R. (2007). Prenatal exposure to valproic acid disturbs the enkephalinergic system functioning, basal hedonic tone, and emotional responses in an animal model of autism. Psychopharmacology, 193(4), 547–555. https://doi.org/10.1007/s00213-007-0795-ySheng, M. & Kim, E. (2011). The postsynaptic organization of synapses. Cold Spring Harb. Perspect., 3(a005678).Silverman, J. L., Tolu, S. S., Barkan, C. L., & Crawley, J. N. (2010). Repetitive Self-Grooming Behavior in the BTBR Mouse Model of Autism is Blocked by the mGluR5 Antagonist MPEP. Neuropsychopharmacology, 35(4), 976. https://doi.org/10.1038/NPP.2009.201Spooren, W., Lindemann, L., Ghosh, A., & Santarelli, L. (2012). Synapse dysfunction in autism : a molecular medicine approach to drug discovery in neurodevelopmental disorders. Trends in Pharmacological Sciences, 33(12), 669–684. https://doi.org/10.1016/j.tips.2012.09.004Stromland, K., Nordin, V., Miller, M., Akerstrom, B., & Gillberg, C. (1994). Autism in thalidomide embryopathy: a population study. Developmental Medicine & Child Neurology, 36, 351–356.Tang, S., Terzic, B., Wang, I.-T. J., Sarmiento, N., Sizov, K., Cui, Y., Takano, H., Marsh, E. D., Zhou, Z., & Coulter, D. A. (2019). Altered NMDAR signaling underlies autistic-like features in mouse models of CDKL5 deficiency disorder. Nature Communications, 10(1). https://doi.org/10.1038/S41467-01910689-WTashiro, Y., Oyabu, A., Imura, Y., Uchida, A., Narita, N., & Narita, M. (2011). Morphological abnormalities of embryonic cranial nerves after in utero exposure to valproic acid: implications for the pathogenesis of autism with multiple developmental anomalies. International Journal of Developmental Neuroscience, 29(4), 359–364. https://doi.org/10.1016/j.ijdevneu.2011.03.008Vanderschuren, L. J. M. J., Achterberg, E. J. M., & Trezza, V. (2016). The neurobiology of social play and its rewarding value in rats. Neuroscience & Biobehavioral Reviews, 70. https://doi.org/10.1016/j.neubiorev.2016.07.025Vasa, R., & Mazurek, M. (2015). An update on anxiety in youth with autism spectrum disorders. Current Opinion in Psychiatry, 28(2), 83–90. https://doi.org/10.1097/YCO.0000000000000133Vorstman, J. A. S., Parr, J. R., Moreno-De-Luca, D., Anney, R. J. L., Nurnberger, J. I., & Hallmayer, J. F. (2017). Autism genetics: opportunities and challenges for clinical translation. Nature Reviews. Genetics, 18(6), 362–376. https://doi.org/10.1038/NRG.2017.4Whitehouse, C. M., & Lewis, M. H. (2015). Repetitive Behavior in Neurodevelopmental Disorders: Clinical and Translational Findings. The Behavior Analyst, 38(2), 163. https://doi.org/10.1007/S40614-0150029-2Williams, P., & Hersh, J. (1997). A male with fetal valproate syndrome and autism. Developmental Medicine & Child Neurology, 39, 632–634.Wu, L. J., Toyoda, H., Zhao, M. G., Lee, Y. S., Tang, J., Ko, S. W., Yong, H. J., Shum, F. W. F., Zerbinatti, C. v., Bu, G., Wei, F., Xu, T. le, Muglia, L. J., Chen, Z. F., Auberson, Y. P., Kaang, B. K., & Zhuo, M. (2005). Upregulation of forebrain NMDA NR2B receptors contributes to behavioral sensitization after inflammation. Journal of Neuroscience, 25(48), 11107–11116. https://doi.org/10.1523/JNEUROSCI.1678-05.2005Xu, J. Y., Xia, Q. Q., & Xia, J. (2012). A review on the current neuroligin mouse models. Sheng Li Xue Bao, 64, 550–562.Yang, E. J., Ahn, S., Lee, K., Mahmood, U., & Kim, H. S. (2016). Early behavioral abnormalities and perinatal alterations of PTEN/AKT pathway in valproic acid autism model mice. PLoS ONE, 11(4). https://doi.org/10.1371/journal.pone.0153298Yang, M., Silverman, J. L., & Crawley, J. N. (2011). Automated three-chambered social approach task for mice. Current Protocols in Neuroscience, SUPPL. 56. https://doi.org/10.1002/0471142301.NS0826S56Yu, Y., Chaulagain, A., Pedersen, S., Lydersen, S., Leventhal, B., Szatmari, P., Aleksic, B., Ozaki, N., & Skokauskas, N. (2020). Pharmacotherapy of restricted/repetitive behavior in autism spectrum disorder:a systematic review and meta-analysis. BMC Psychiatry, 20(1). https://doi.org/10.1186/S12888-020-2477-9Zoghbi, H., & Bear, M. (2012). Synaptic Dysfunction in Neurodevelopmental Intellectual Disabilities. Cold Spring Harb. Perspect. Biol., 4(3), 1–22. https://doi.org/10.1101/cshperspect.a009886InvestigadoresORIGINAL1012400569.2022.pdf1012400569.2022.pdfTesis de Maestría en Neurocienciasapplication/pdf1950837https://repositorio.unal.edu.co/bitstream/unal/82248/2/1012400569.2022.pdf5f6031885220bc9782c45584086b22c0MD52LICENSElicense.txtlicense.txttext/plain; charset=utf-84675https://repositorio.unal.edu.co/bitstream/unal/82248/3/license.txtb577153cc0e11f0aeb5fc5005dc82d8aMD53unal/82248oai:repositorio.unal.edu.co:unal/822482023-01-11 14:23:45.727Repositorio Institucional Universidad Nacional de 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

Aproximación comportamental y glutamatérgica de un modelo de roedor del trastorno del espectro autista por exposición prenatal a ácido valproico

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