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Órgano Oficial del Instituto Nacional de Psiquiatría Ramón de la Fuente Muñiz

2006, Número 5

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Salud Mental 2006; 29 (5)


Papel de los receptores de glutamato durante la diferenciación neuronal

Moreno-González G, Zarain-Herzberg A

Idioma: Español
Referencias bibliográficas: 70
Paginas: 38-48
Archivo PDF: 158.43 Kb.


RESUMEN

El L-glutamato (Glu) es el principal neurotransmisor excitador del Sistema Nervioso Central (SNC) y ejerce su función por medio de receptores (GluRs) que se clasifican en dos grandes superfamilias. La primera la forman canales iónicos activados por ligando o receptores de glutamato ionotrópicos (iGluRs) permeables a Ca2+, Na+ y K+. Estos se han clasificado en tres familias con base en datos farmacológicos y electrofisiológicos: los receptores para el α-amino-3-hidroxi-5-metil-4-isoxazol propionato (AMPA); los receptores para kainato (KA); y los receptores para N-metil-Daspartato (NMDA). A la segunda superfamilia pertenecen los GluRs acoplados a segundos mensajeros (inositol 3-fosfato, diacilglicerol y AMP cíclico), también llamados receptores metabotrópicos (mGluRs).
La importancia del estudio de los GluRs en el SNC se centra en el papel que estos cumplen en diversas enfermedades neurodegenerativas, como la corea de Huntington, la enfermedad de Parkinson, la enfermedad de Alzheimer, la esclerosis lateral amiotrófica, los accidentes vasculares cerebrales, la epilepsia, la demencia por VIH, la enfermedad de Creutzfeld-Jacob y la hipoglicemia, así como en enfermedades psiquiátricas como la esquizofrenia, la depresión, los trastornos de ansiedad y la enfermedad por estrés postraumático. Además, el Glu, al actuar mediante diversos receptores, desempeña un papel fundamental en los procesos que involucran la diferenciación neuronal y el desarrollo del SNC. Se sabe que existe una expresión diferencial de la gran variedad de subunidades de iGluRs y mGluRs durante la diferenciación y el desarrollo del SNC, la cual depende tanto de su localización en el SNC como de la etapa del desarrollo neuronal.
Durante la neurogénesis, se encuentran niveles altos de Glu en las áreas de desarrollo del SNC que, por activación de diferentes receptores, dan lugar a una señalización por segundos mensajeros, una variación en las concentraciones de calcio intracelular [Ca2+]i y la expresión de genes importantes en la regulación del ciclo celular; lo anterior promueve el crecimiento y la diferenciación celular, así como la sobrevida neuronal. Además, el Glu favorece el crecimiento del árbol presináptico y la ramificación dendrítica postsináptica, lo que a su vez promueve el establecimiento y el mantenimiento sinápticos. Esto, junto con la eliminación sináptica y el silenciamiento de receptores, es un mecanismo fundamental para establecer redes neuronales maduras. El Glu también es importante para la formación de sinapsis inhibitorias durante el desarrollo.
La activación de GluRs promueve el crecimiento de las dendritas de las neuronas motoras. Se ha observado que los cambios bifásicos en la [Ca2+]i, en respuesta a Glu, se correlacionan con las fases facilitadoras e inhibidoras del crecimiento dendrítico. La evidencia acumulada indica que, dependiendo de su concentración extracelular y del tipo de receptor estimulado, el Glu puede favorecer o detener la migración neuronal, que es fundamental para el desarrollo del SNC.
Aunque hasta el momento los receptores de tipo NMDA son los más estudiados en el desarrollo del SNC, en esta revisión se muestra la importancia de la gran variedad de GluRs, tanto ionotrópicos como metabotrópicos, en los procesos mencionados anteriormente y que, según su patrón de expresión diferencial durante el desarrollo, cumplen un papel importante en el proceso de formación de las diferentes regiones del SNC desde la embriogénesis hasta la vida adulta.


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