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A High-throughput Calcium-flux Assay to Study NMDA-receptors with Sensitivity to Glycine/D-serine and Glutamate
Published on: July 10, 2018
Los receptores NMDA median la acumulación de calcio en la mielina durante la isquemia química
1Ottawa Health Research Institute, Division of Neuroscience and Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa, Ontario K1Y 4K9, Canada.
Nature
|December 24, 2005
Resumen
La mielina del sistema nervioso central puede acumular calcio durante la isquemia, independientemente de los oligodendrocitos. Los receptores de N-metil-d-aspartato (NMDA) en la mielina median este aumento de calcio, lo que sugiere un nuevo objetivo terapéutico para las enfermedades desmielinizantes.
Área de la Ciencia:
- La neurociencia es la neurociencia.
- Biología celular Biología celular.
- La neurodegeneración es una neurodegeneración.
Sus antecedentes:
- La mielina del sistema nervioso central (SNC), producida por los oligodendrocitos, es crucial para la rápida conducción del impulso nervioso.
- El daño y la pérdida de mielina son características de numerosos trastornos neurológicos, que conducen a una discapacidad significativa.
- Los mecanismos que inician el daño de la mielina son poco conocidos, a menudo asumiendo que refleja el destino de los oligodendrocitos.
Objetivo del estudio:
- Investigar el papel de los receptores de glutamato N-metil-d-aspartato (NMDA) en la mediación de la acumulación de calcio dentro de la mielina del SNC durante la isquemia química.
- Para determinar si la mielina puede responder de forma independiente a los estímulos perjudiciales.
- Explorar posibles objetivos terapéuticos para las enfermedades desmielinizantes.
Principales métodos:
- Se utilizó la microscopía de dos fotones para obtener imágenes del indicador de calcio X-rhod-1 en los nervios ópticos de ratas adultas.
- Aplicó varios antagonistas de los receptores NMDA y AMPA/kainato (MK-801, ácido 7-clorokinurénico, d-AP5, NBQX, NVP-AAM077, ifenprodil).
- Se realizó inmunohistoquímica e inmunoprecipitación para detectar las subunidades del receptor NMDA (NR1, NR2, NR3) en la mielina.
Principales resultados:
- Los antagonistas de los receptores NMDA, pero no los antagonistas de AMPA / kainato, bloquearon significativamente el aumento de calcio inducido por isquemia en la mielina.
- El antagonismo del receptor NMDA redujo sustancialmente el daño ultrastructural a la mielina causado por isquemia in vitro.
- Todas las subunidades necesarias del receptor NMDA se detectaron en la mielina, lo que indica la presencia de un receptor funcional.
Conclusiones:
- La vaina de mielina madura puede responder a estímulos perjudiciales, como la isquemia, independientemente del oligodendrocito progenitor.
- Los receptores NMDA ubicados dentro de la vaina de mielina median la acumulación de calcio durante la isquemia, lo que representa una nueva vía de señalización axomielínica.
- Dirigirse a los receptores NMDA mielínicos ofrece una estrategia terapéutica potencial para enfermedades desmielinizantes como la esclerosis múltiple y el neurotrauma.
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