Evaluación del efecto del extracto de zanthoxylum martinicense sobre la expresión de apoe, lrp, glast y glt-1 en modelo de astrocitos y en ratones 3x tg-ad
ilustraciones, diagramas
- Autores:
-
Lopez-Cano, Juan Guillermo
- Tipo de recurso:
- Fecha de publicación:
- 2023
- Institución:
- Universidad Nacional de Colombia
- Repositorio:
- Universidad Nacional de Colombia
- Idioma:
- spa
- OAI Identifier:
- oai:repositorio.unal.edu.co:unal/84372
- Palabra clave:
- 570 - Biología::572 - Bioquímica
570 - Biología::573 - Sistemas fisiológicos específicos en animales, histología regional y fisiología en los animales
580 - Plantas::582 - Plantas destacadas por características vegetativas y flores
610 - Medicina y salud::615 - Farmacología y terapéutica
610 - Medicina y salud::616 - Enfermedades
Medicina alternativa
Alternative medicine
Neuropathy
Medicinal plant
Neuropatía
Plantas medicinales
Alzheimer
Zanthoxylum martinicense
ApoE
GLT-1
GLT1
GLAST
Astrocitos
Excitotoxicidad
Glutamato
Transportadores
Alzheimer
Zanthoxylum martinicense
ApoE
GLT-1
GLT1
GLAST
Astrocytes
Excitotoxicity
Glutamate
Transporters
- Rights
- openAccess
- License
- Atribución-NoComercial-SinDerivadas 4.0 Internacional
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| dc.title.spa.fl_str_mv |
Evaluación del efecto del extracto de zanthoxylum martinicense sobre la expresión de apoe, lrp, glast y glt-1 en modelo de astrocitos y en ratones 3x tg-ad |
| dc.title.translated.eng.fl_str_mv |
Evaluation of the effect of Zanthoxylum martinicense extract over the expression of ApoE, LRP, GLAST y GLT-1 in an astrocyte model and 3x Tg-AD mice |
| title |
Evaluación del efecto del extracto de zanthoxylum martinicense sobre la expresión de apoe, lrp, glast y glt-1 en modelo de astrocitos y en ratones 3x tg-ad |
| spellingShingle |
Evaluación del efecto del extracto de zanthoxylum martinicense sobre la expresión de apoe, lrp, glast y glt-1 en modelo de astrocitos y en ratones 3x tg-ad 570 - Biología::572 - Bioquímica 570 - Biología::573 - Sistemas fisiológicos específicos en animales, histología regional y fisiología en los animales 580 - Plantas::582 - Plantas destacadas por características vegetativas y flores 610 - Medicina y salud::615 - Farmacología y terapéutica 610 - Medicina y salud::616 - Enfermedades Medicina alternativa Alternative medicine Neuropathy Medicinal plant Neuropatía Plantas medicinales Alzheimer Zanthoxylum martinicense ApoE GLT-1 GLT1 GLAST Astrocitos Excitotoxicidad Glutamato Transportadores Alzheimer Zanthoxylum martinicense ApoE GLT-1 GLT1 GLAST Astrocytes Excitotoxicity Glutamate Transporters |
| title_short |
Evaluación del efecto del extracto de zanthoxylum martinicense sobre la expresión de apoe, lrp, glast y glt-1 en modelo de astrocitos y en ratones 3x tg-ad |
| title_full |
Evaluación del efecto del extracto de zanthoxylum martinicense sobre la expresión de apoe, lrp, glast y glt-1 en modelo de astrocitos y en ratones 3x tg-ad |
| title_fullStr |
Evaluación del efecto del extracto de zanthoxylum martinicense sobre la expresión de apoe, lrp, glast y glt-1 en modelo de astrocitos y en ratones 3x tg-ad |
| title_full_unstemmed |
Evaluación del efecto del extracto de zanthoxylum martinicense sobre la expresión de apoe, lrp, glast y glt-1 en modelo de astrocitos y en ratones 3x tg-ad |
| title_sort |
Evaluación del efecto del extracto de zanthoxylum martinicense sobre la expresión de apoe, lrp, glast y glt-1 en modelo de astrocitos y en ratones 3x tg-ad |
| dc.creator.fl_str_mv |
Lopez-Cano, Juan Guillermo |
| dc.contributor.advisor.none.fl_str_mv |
Arboleda Bustos, Gonzalo Humberto |
| dc.contributor.author.none.fl_str_mv |
Lopez-Cano, Juan Guillermo |
| dc.contributor.financer.none.fl_str_mv |
Colciencias |
| dc.contributor.researchgroup.spa.fl_str_mv |
Grupo de Neurociencias-Universidad Nacional de Colombia Muerte Celular |
| dc.subject.ddc.spa.fl_str_mv |
570 - Biología::572 - Bioquímica 570 - Biología::573 - Sistemas fisiológicos específicos en animales, histología regional y fisiología en los animales 580 - Plantas::582 - Plantas destacadas por características vegetativas y flores 610 - Medicina y salud::615 - Farmacología y terapéutica 610 - Medicina y salud::616 - Enfermedades |
| topic |
570 - Biología::572 - Bioquímica 570 - Biología::573 - Sistemas fisiológicos específicos en animales, histología regional y fisiología en los animales 580 - Plantas::582 - Plantas destacadas por características vegetativas y flores 610 - Medicina y salud::615 - Farmacología y terapéutica 610 - Medicina y salud::616 - Enfermedades Medicina alternativa Alternative medicine Neuropathy Medicinal plant Neuropatía Plantas medicinales Alzheimer Zanthoxylum martinicense ApoE GLT-1 GLT1 GLAST Astrocitos Excitotoxicidad Glutamato Transportadores Alzheimer Zanthoxylum martinicense ApoE GLT-1 GLT1 GLAST Astrocytes Excitotoxicity Glutamate Transporters |
| dc.subject.decs.spa.fl_str_mv |
Medicina alternativa |
| dc.subject.lemb.eng.fl_str_mv |
Alternative medicine Neuropathy Medicinal plant |
| dc.subject.lemb.spa.fl_str_mv |
Neuropatía Plantas medicinales |
| dc.subject.proposal.spa.fl_str_mv |
Alzheimer Zanthoxylum martinicense ApoE GLT-1 GLT1 GLAST Astrocitos Excitotoxicidad Glutamato Transportadores |
| dc.subject.proposal.eng.fl_str_mv |
Alzheimer Zanthoxylum martinicense ApoE GLT-1 GLT1 GLAST Astrocytes Excitotoxicity Glutamate Transporters |
| description |
ilustraciones, diagramas |
| publishDate |
2023 |
| dc.date.accessioned.none.fl_str_mv |
2023-07-31T14:23:20Z |
| dc.date.available.none.fl_str_mv |
2023-07-31T14:23:20Z |
| dc.date.issued.none.fl_str_mv |
2023-07-30 |
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Trabajo de grado - Maestría |
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info:eu-repo/semantics/masterThesis |
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https://repositorio.unal.edu.co/handle/unal/84372 |
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Universidad Nacional de Colombia |
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Repositorio Institucional Universidad Nacional de Colombia |
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https://repositorio.unal.edu.co/ |
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https://repositorio.unal.edu.co/handle/unal/84372 https://repositorio.unal.edu.co/ |
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Almad, A., & Maragakis, N. J. (2018). A stocked toolbox for understanding the role of astrocytes in disease. In Nature Reviews Neurology (Vol. 14, Issue 6, pp. 351–362). Nature Publishing Group. https://doi.org/10.1038/s41582-018-0010-2 Almad, A., & Maragakis, N. J. (2018). A stocked toolbox for understanding the role of astrocytes in disease. In Nature Reviews Neurology (Vol. 14, Issue 6, pp. 351–362). Nature Publishing Group. https://doi.org/10.1038/s41582-018-0010-2 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 2018 33:3, 33(3), 569–579. https://doi.org/10.1007/S12640-017-9845-3 Ben Haim, L., & Rowitch, D. H. (2016). Functional diversity of astrocytes in neural circuit regulation. Nature Reviews Neuroscience 2016 18:1, 18(1), 31–41. https://doi.org/10.1038/nrn.2016.159 Benarroch, E. E. (2010). Glutamate transporters. Neurology, 74(3), 259–264. https://doi.org/10.1212/WNL.0B013E3181CC89E3 Bezprozvanny, I., & Mattson, M. P. (2008). Neuronal calcium mishandling and the pathogenesis of Alzheimer’s disease. Trends in Neurosciences, 31(9), 454–463. https://doi.org/10.1016/J.TINS.2008.06.005 Bustos-Rangel, A. (2021). Búsqueda de agonistas LXR en plantas colombianas con potencial terapéutico para la enfermedad de Alzheimer [Nacional de Colombia]. https://repositorio.unal.edu.co/handle/unal/80277 Emonard, H., Théret, L., Bennasroune, A. H., & Dedieu, S. (2014). Regulation of LRP-1 expression: make the point. Pathologie-Biologie, 62(2), 84–90. https://doi.org/10.1016/J.PATBIO.2014.02.002 Esposito, Z., Belli, L., Toniolo, S., Sancesario, G., Bianconi, C., & Martorana, A. (2013). Amyloid β, Glutamate, Excitotoxicity in Alzheimer’s Disease: Are We on the Right Track? CNS Neuroscience & Therapeutics, 19(8), 549. https://doi.org/10.1111/CNS.12095 Fontana, A. C. K. (2015). Current approaches to enhance glutamate transporter function and expression. Journal of Neurochemistry, 134(6), 982–1007. https://doi.org/10.1111/JNC.13200 Galland, F., Seady, M., Taday, J., Smaili, S. S., Gonçalves, C. A., & Leite, M. C. (2019). Astrocyte culture models: Molecular and function characterization of primary culture, immortalized astrocytes and C6 glioma cells. Neurochemistry International, 131, 104538. https://doi.org/10.1016/j.neuint.2019.104538 Go, G. W., & Mani, A. (2012). Low-Density Lipoprotein Receptor (LDLR) Family OrchestratesCholesterol Homeostasis. The Yale Journal of Biology and Medicine, 85(1), 19. /pmc/articles/PMC3313535/ González-Reyes, R., Nava-Mesa, M., Ariza-Salamanca, D., Mora-Muñoz, L., & Vargas-Sánchez, K. (2017). Involvement of astrocytes in Alzheimer’s disease from a neuroinflammatory and oxidative stress perspective. Frontiers in Molecular Neuroscience, 10. https://doi.org/10.3389/fnmol.2017.00427 Hiebl, V., Ladurner, A., Latkolik, S., & Dirsch, V. M. (2018). Natural products as modulators of the nuclear receptors and metabolic sensors LXR, FXR and RXR. Biotechnology Advances, 36(6), 1657–1698. https://doi.org/10.1016/J.BIOTECHADV.2018.03.003 Hodson, R. (2018). Alzheimer’s disease. Nature, 559(7715), S1. https://doi.org/10.1038/D41586-018-05717-6 Hong, D. Y., Lee, D. H., Lee, J. Y., Lee, E. C., Park, S. W., Lee, M. R., & Oh, J. S. (2022). Relationship between Brain Metabolic Disorders and Cognitive Impairment: LDL Receptor Defect. International Journal of Molecular Sciences, 23(15). https://doi.org/10.3390/IJMS23158384 Jeremic, D., Jiménez-Díaz, L., & Navarro-López, J. D. (2021). Past, present and future of therapeutic strategies against amyloid-β peptides in Alzheimer’s disease: a systematic review. Ageing Research Reviews, 72. https://doi.org/10.1016/J.ARR.2021.101496 Jonathan, M. C., Adrián, S. H., & Gonzalo, A. (2021). Type II nuclear receptors with potential role in Alzheimer disease. Molecular Aspects of Medicine, 100940. https://doi.org/10.1016/j.mam.2020.100940 Lee, H. G., Wheeler, M. A., & Quintana, F. J. (2022). Function and therapeutic value of astrocytes in neurological diseases. Nature Reviews. Drug Discovery, 21(5), 339. https://doi.org/10.1038/S41573-022-00390-X Leik, C. E., Carson, N. L., Hennan, J. K., Basso, M. D., Liu, Q. Y., Crandall, D. L., & Nambi, P. (2007). GW3965, a synthetic liver X receptor (LXR) agonist, reduces angiotensin II-mediated pressor responses in Sprague–Dawley rats. British Journal of Pharmacology, 151(4), 450. https://doi.org/10.1038/SJ.BJP.0707241 Lemberg, A., & Fernández, M. A. (2009). Hepatic encephalopathy, ammonia, glutamate, glutamine and oxidative stress. Annals of Hepatology, 8(2), 95–102. https://doi.org/10.1016/S1665-2681(19)31785-5 Li, C., Zhao, R., Gao, K., Wei, Z., Yaoyao Yin, M., Ting Lau, L., Chui, D., & Cheung Hoi Yu, A. (2011). Astrocytes: Implications for Neuroinflammatory Pathogenesis of Alzheimers Disease. Current Alzheimer Research, 8(1), 67–80. https://doi.org/10.2174/156720511794604543 Li, Z., Shue, F., Zhao, N., Shinohara, M., & Bu, G. (2020). APOE2: protective mechanism and therapeutic implications for Alzheimer’s disease. Molecular Neurodegeneration, 15(1). https://doi.org/10.1186/S13024-020-00413-4 Liao, F., Yoon, H., & Kim, J. (2017). Apolipoprotein E metabolism and functions in brain and its role in Alzheimer’s disease. Current Opinion in Lipidology, 28(1), 60. https://doi.org/10.1097/MOL.0000000000000383 Maragakis, N. J., & Rothstein, J. D. (2006). Mechanisms of Disease: Astrocytes in neurodegenerative disease. In Nature Clinical Practice Neurology (Vol. 2, Issue 12, pp. 679–689). Nat Clin Pract Neurol. https://doi.org/10.1038/ncpneuro0355 Matias, I., Morgado, J., & Gomes, F. C. A. (2019). Astrocyte Heterogeneity: Impact to Brain Aging and Disease. In Frontiers in Aging Neuroscience (Vol. 11). Frontiers Media S.A. https://doi.org/10.3389/fnagi.2019.00059 McConnell, H. L., & Mishra, A. (2022). Cells of the Blood-brain Barrier: an Overview of the Neurovascular Unit in Health and Disease. Methods in Molecular Biology (Clifton, N.J.), 2492, 3. https://doi.org/10.1007/978-1-0716-2289-6_1 Muñoz-Cabrera, J. M. (2015). Efecto del Bexaroteno sobre la plasticidad en la sinapsis comisural CA3-CA1 en un modelo murino de enfermedad de Alzheimer. Universidad Nacional de Colombia Muñoz-Cabrera, J. M., Sandoval-Hernández, A. G., Niño, A., Báez, T., Bustos-Rangel, A., Cardona-Gómez, G. P., Múnera, A., & Arboleda, G. (2019). Bexarotene therapy ameliorates behavioral deficits and induces functional and molecular changes in very-old Triple Transgenic Mice model of Alzheimer´s disease. PLOS ONE, 14(10), e0223578. https://doi.org/10.1371/JOURNAL.PONE.0223578 Namjoshi, D. R., Martin, G., Donkin, J., Wilkinson, A., Stukas, S., Fan, J., Carr, M., Tabarestani, S., Wuerth, K., Hancock, R. E. W., & Wellington, C. L. (2013). The Liver X Receptor Agonist GW3965 Improves Recovery from Mild Repetitive Traumatic Brain Injury in Mice Partly through Apolipoprotein E. PLOS ONE, 8(1), e53529. https://doi.org/10.1371/JOURNAL.PONE.0053529 Pajarillo, E., Rizor, A., Lee, J., Aschner, M., & Lee, E. (2019a). The role of astrocytic glutamate transporters GLT-1 and GLAST in neurological disorders: Potential targets for neurotherapeutics. Neuropharmacology, 161, 107559. https://doi.org/10.1016/j.neuropharm.2019.03.002 Pajarillo, E., Rizor, A., Lee, J., Aschner, M., & Lee, E. (2019b). The role of astrocytic glutamate transporters GLT-1 and GLAST in neurological disorders: Potential targets for neurotherapeutics. Neuropharmacology, 161. https://doi.org/10.1016/j.neuropharm.2019.03.002 Park, S. H., Lee, J. Y., Jhee, K. H., & Yang, S. A. (2020). Amyloid-ß peptides inhibit the expression of AQP4 and glutamate transporter EAAC1 in insulin-treated C6 glioma cells. Toxicology Reports, 7, 1083–1089. https://doi.org/10.1016/j.toxrep.2020.08.032 Peng, M., Ling, X., Song, R., Gao, X., Liang, Z., Fang, F., & Cang, J. (2019). Upregulation of GLT-1 via PI3K/Akt Pathway Contributes to Neuroprotection Induced by Dexmedetomidine. Frontiers in Neurology, 10(SEP). https://doi.org/10.3389/FNEUR.2019.01041 Pérez Silva, A. (2023). Evaluación del potencial terapéutico del extracto vegetal Zanthoxylum martinicense asociado a la actividad agonista de LXR en el modelo murino de enfermedad de Alzheimer (3xTg-AD). Universidad Nacional de Colombia. https://repositorio.unal.edu.co/handle/unal/83985 Prada, S. I., Takeuchi, Y., & Ariza, Y. (2014). Costo monetario del tratamiento de la enfermedad de Alzheimer en Colombia Monetary cost of treatment for Alzheimer’s disease in Colombia Artículo original. Acta Neurol Colomb, 30(4), 247–255. Rebec, G. V. (2013). Dysregulation of Corticostriatal Ascorbate Release and Glutamate Uptake in Transgenic Models of Huntington’s Disease. Antioxidants & Redox Signaling, 19(17), 2115. https://doi.org/10.1089/ARS.2013.5387 Rezaee, N., Fernando, W. M. A. D. B., Hone, E., Sohrabi, H. R., Johnson, S. K., Gunzburg, S., & Martins, R. N. (2021). Potential of Sorghum Polyphenols to Prevent and Treat Alzheimer’s Disease: A Review Article. Frontiers in Aging Neuroscience, 13, 603. https://doi.org/10.3389/FNAGI.2021.729949/BIBTEX Rodríguez-Arellano, J. J., Parpura, V., Zorec, R., & Verkhratsky, A. (2016). Astrocytes in physiological aging and Alzheimer’s disease. In Neuroscience (Vol. 323, pp. 170–182). Elsevier Ltd. https://doi.org/10.1016/j.neuroscience.2015.01.007 Rodríguez-Giraldo, M., González-Reyes, R. E., Ramírez-Guerrero, S., Bonilla-Trilleras, C. E., Guardo-Maya, S., & Nava-Mesa, M. O. (2022). Astrocytes as a Therapeutic Target in Alzheimer’s Disease–Comprehensive Review and Recent Developments. International Journal of Molecular Sciences 2022, Vol. 23, Page 13630, 23(21), 13630. https://doi.org/10.3390/IJMS232113630 Sahng, W. P., Moon, Y. A., & Horton, J. D. (2004). Post-transcriptional Regulation of Low Density Lipoprotein Receptor Protein by Proprotein Convertase Subtilisin/Kexin Type 9a in Mouse Liver. Journal of Biological Chemistry, 279(48), 50630–50638. https://doi.org/10.1074/JBC.M410077200 Sandoval-Hernández, A. G., Buitrago, L., Moreno, H., Cardona-Gómez, G. P., & Arboleda, G. (2015). Role of Liver X Receptor in AD Pathophysiology. PLOS ONE, 10(12), e0145467. https://doi.org/10.1371/JOURNAL.PONE.0145467 Sandoval-Hernández, A. G., Restrepo, A., Cardona-Gómez, G. P., & Arboleda, G. (2016). LXR activation protects hippocampal microvasculature in very old triple transgenic mouse model of Alzheimer’s disease. Neuroscience Letters, 621, 15–21. https://doi.org/10.1016/J.NEULET.2016.04.007 Simpson, J. E., Ince, P. G., Lace, G., Forster, G., Shaw, P. J., Matthews, F., Savva, G., Brayne, C., & Wharton, S. B. (2010). Astrocyte phenotype in relation to Alzheimer-type pathology in the ageing brain. Neurobiology of Aging, 31(4), 578–590. https://doi.org/10.1016/J.NEUROBIOLAGING.2008.05.015 Sofroniew, M. V., & Vinters, H. V. (2010). Astrocytes: Biology and pathology. In Acta Neuropathologica (Vol. 119, Issue 1, pp. 7–35). Acta Neuropathol. https://doi.org/10.1007/s00401-009-0619-8 Soni, N., Reddy, B. V. K., & Kumar, P. (2014). GLT-1 transporter: An effective pharmacological target for various neurological disorders. Pharmacology Biochemistry and Behavior, 127, 70–81. https://doi.org/10.1016/j.pbb.2014.10.001 Verkhratsky, A., Olabarria, M., Noristani, H. N., Yeh, C. Y., & Rodriguez, J. J. (2010). Astrocytes in Alzheimer’s Disease. Neurotherapeutics, 7(4), 399–412. https://doi.org/10.1016/j.nurt.2010.05.017 von Bartheld, C. S., Bahney, J., & Herculano-Houzel, S. (2016). The search for true numbers of neurons and glial cells in the human brain: A review of 150 years of cell counting. Journal of Comparative Neurology, 524(18), 3865–3895. https://doi.org/10.1002/CNE.24040 Wood, O. W. G., Yeung, J. H. Y., Faull, R. L. M., & Kwakowsky, A. (2022). EAAT2 as a therapeutic research target in Alzheimer’s disease: A systematic review. Frontiers in Neuroscience, 16, 952096. https://doi.org/10.3389/fnins.2022.952096 Zhang, X., Lao, K., Qiu, Z., Rahman, M. S., Zhang, Y., & Gou, X. (2019). Potential Astrocytic Receptors and Transporters in the Pathogenesis of Alzheimer’s Disease. Journal of Alzheimer’s Disease : JAD, 67(4), 1109–1122. https://doi.org/10.3233/JAD-181084 Ruiz González, J. (2021). Evaluación del potencial terapéutico de un extracto de raíz de Zanthoxylum caribaeum en un modelo triple transgénico de Enfermedad de Alzheimer. Universidad Nacional de Colombia Caicedo Díaz, J. (2021). Evaluación del potencial terapéutico de agonistas sintéticos y naturales de LXR (GW3965 y Nectandra reticulata) en el modelo murino 3xTg-AD de la enfermedad de Alzheimer. Universidad Nacional de Colombia. Prillaman, M. (2022). Alzheimer's drug slows mental decline in trial-but is it a breakthrough?. Nature |
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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_abf2Arboleda Bustos, Gonzalo Humberto8d01100986b4e816de54bb4d3f52f1f0Lopez-Cano, Juan Guillermoae135867404dbed1cd4cc96ab553974bColcienciasGrupo de Neurociencias-Universidad Nacional de ColombiaMuerte Celular2023-07-31T14:23:20Z2023-07-31T14:23:20Z2023-07-30https://repositorio.unal.edu.co/handle/unal/84372Universidad Nacional de ColombiaRepositorio Institucional Universidad Nacional de Colombiahttps://repositorio.unal.edu.co/ilustraciones, diagramasEl aumento no regulado de la excitación neuronal y del ingreso de calcio a la célula, conocido como excitotoxicidad y causado por un exceso de glutamato (ya sea en tiempo de permanencia y/o en concentración) en la hendidura sináptica, o por acúmulos de Aβ en el espacio extracelular en contextos de Alzheimer, ha sido considerado como uno de los posibles mecanismos moleculares que derivan en la muerte de neuronas del hipocampo en el desarrollo de la enfermedad de Alzheimer (EA). Los extractos vegetales presentan características químicas estructurales que amplían el espectro de ligandos o compuestos con actividad neuroprotectora, y dada esa diversidad química han ganado importancia en la búsqueda de alternativas terapéuticas a enfermedades neurodegenerativas como la EA convirtiéndolos en sustancias privilegiadas multidiana. En este trabajo se evaluó el efecto de un extracto etanólico de raíz de Zanthoxylum martinicense sobre la expresión de las proteínas astrocitarias responsables de la regulación del glutamato en la hendidura sináptica, adicionalmente se evaluó el cambio en otras proteínas de interés en contextos de la EA dada la actividad agonista LXRβ de este extracto demostrada previamente en nuestro grupo de investigación. Mediante técnicas de inmunología y de cuantificación de proteínas totales, se evaluó el cambio en la expresión de las proteínas LRP, APOE (que tienen un rol protagónico en la homeostasis de Aβ en el sistema nervioso central) y de los transportadores de glutamato GLAST (EAAT1) y GLT-1 (EAAT2), en cultivos in vitro de la línea U87-MG empleado como modelo de astrocitos y en un modelo in vivo de ratones 3xTg-AD que fueron tratados con el extracto de Zanthoxylum martinicense. El resultado muestra que el tratamiento con este extracto específicamente tiene un efecto dosis dependiente en el aumento de la expresión de las proteínas ya mencionadas excepto LRP. El aumento en la expresión de APOE, GLAST y GLT1 tiene un potencial efecto neuroprotector por la posible mejora de la remoción de Aβ y en el incremento en la eficiencia de la retoma del glutamato sináptico evitando eventos de excitotoxidad, y puede pensarse que sean una parte del sustento molecular que soporta la recuperación de la memoria espacial en ratones 3xTg-AD tratados con el extracto. (Texto tomado de la fuente)The dysregulated increase of neuronal excitation and calcium entry into the neuron, known as excitotoxicity, after a glutamate excess in the synaptic cleft or because of the Aβ aggregates in the extracellular matrix in Alzheimer’s disease (AD), has been considered as one of the possible molecular mechanisms driving neurodegeneration in the hippocampus during progression of AD. Vegetable extracts exhibit structural chemical features that enlarge the spectrum of ligands or compounds with neuroprotective capacity. According to this chemical diversity, they have emerged as protagonists in the search for therapeutic alternatives to neurodegenerative diseases like Alzheimer, and make them privileged multitarget compounds. In this research, we tested the effect of an ethanolic Zanthoxylum martinicense root’s extract on the expression of astrocytic proteins responsible for glutamate reuptake in the synaptic cleft. Additionally, because previous research in our lab demonstrated an LXRβ agonist activity of the extract, we evaluate the change in additional proteins related to AD. By using immunology tools and total protein quantification procedures, we probed changes in the expression of LRP, APOE (with a main role in the Aβ homeostasis in the central nervous system) and for the astrocytic glutamate transporters GLAST (EAAT1) and GLT-1 (EAAT2), in cultures of U87-MG cell line used as an astrocytic model, and in an in-vivo model of 3xTg-AD mice that were treated with the Zanthoxylum martinicense extract. Our results show that the treatment with this extract has a dose-dependent effect in the upregulation of the above-mentioned proteins, except LRP. The APOE, GLT1, and GLAST upregulation has a potential neuroprotective effect, due to their potential increased in Aβ removal and increased reuptake of synaptic glutamate, therefore avoiding excitotoxicity. We speculate that these effects are a constitutive part of the molecular substrate that supports the spatial memory recovery of 3xTg-AD treated with the extract.MaestríaMagister en NeurocienciasMuerte CelularAlzheimerextractos vegetalesastrocitosexcitotoxicidadglutamatoxxii, 98 páginasapplication/pdfspaUniversidad Nacional de ColombiaBogotá - Medicina - Maestría en NeurocienciasFacultad de MedicinaBogotá,ColombiaUniversidad Nacional de Colombia - Sede Bogotá570 - Biología::572 - Bioquímica570 - Biología::573 - Sistemas fisiológicos específicos en animales, histología regional y fisiología en los animales580 - Plantas::582 - Plantas destacadas por características vegetativas y flores610 - Medicina y salud::615 - Farmacología y terapéutica610 - Medicina y salud::616 - EnfermedadesMedicina alternativaAlternative medicineNeuropathyMedicinal plantNeuropatíaPlantas medicinalesAlzheimerZanthoxylum martinicenseApoEGLT-1GLT1GLASTAstrocitosExcitotoxicidadGlutamatoTransportadoresAlzheimerZanthoxylum martinicenseApoEGLT-1GLT1GLASTAstrocytesExcitotoxicityGlutamateTransportersEvaluación del efecto del extracto de zanthoxylum martinicense sobre la expresión de apoe, lrp, glast y glt-1 en modelo de astrocitos y en ratones 3x tg-adEvaluation of the effect of Zanthoxylum martinicense extract over the expression of ApoE, LRP, GLAST y GLT-1 in an astrocyte model and 3x Tg-AD miceTrabajo de grado - Maestríainfo:eu-repo/semantics/masterThesisinfo:eu-repo/semantics/acceptedVersionTexthttp://purl.org/redcol/resource_type/TMAlmad, A., & Maragakis, N. 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Evaluación del potencial terapéutico de agonistas sintéticos y naturales de LXR (GW3965 y Nectandra reticulata) en el modelo murino 3xTg-AD de la enfermedad de Alzheimer. Universidad Nacional de Colombia.Prillaman, M. (2022). Alzheimer's drug slows mental decline in trial-but is it a breakthrough?. NatureBioprospección del potencial terapéutico de extractos vegetales de las familias laurácea y rutácea asociados a la actividad farmacológica de LXR en un modelo murino de enfermedad de Alzheimer y análisis computacionalColcienciasEstudiantesInvestigadoresMaestrosMedios de comunicaciónPúblico generalLICENSElicense.txtlicense.txttext/plain; charset=utf-85879https://repositorio.unal.edu.co/bitstream/unal/84372/1/license.txteb34b1cf90b7e1103fc9dfd26be24b4aMD51ORIGINAL71786951.2023.pdf71786951.2023.pdfTesis de Maestría en Neurocienciasapplication/pdf2832137https://repositorio.unal.edu.co/bitstream/unal/84372/2/71786951.2023.pdfec1777795b9e383813e4545095d883dfMD52THUMBNAIL71786951.2023.pdf.jpg71786951.2023.pdf.jpgGenerated Thumbnailimage/jpeg6003https://repositorio.unal.edu.co/bitstream/unal/84372/3/71786951.2023.pdf.jpga32a43953da1d21746136ffdbe2b6c6fMD53unal/84372oai:repositorio.unal.edu.co:unal/843722024-08-17 23:12:37.478Repositorio Institucional Universidad Nacional de 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