Glutamate-induced and NMDA receptor-mediated neurodegeneration entails P2Y1 receptor activation

Cell Death & Disease
Ana P SimõesRicardo J Rodrigues

Abstract

Despite the characteristic etiologies and phenotypes, different brain disorders rely on common pathogenic events. Glutamate-induced neurotoxicity is a pathogenic event shared by different brain disorders. Another event occurring in different brain pathological conditions is the increase of the extracellular ATP levels, which is now recognized as a danger and harmful signal in the brain, as heralded by the ability of P2 receptors (P2Rs) to affect a wide range of brain disorders. Yet, how ATP and P2R contribute to neurodegeneration remains poorly defined. For that purpose, we now examined the contribution of extracellular ATP and P2Rs to glutamate-induced neurodegeneration. We found both in vitro and in vivo that ATP/ADP through the activation of P2Y1R contributes to glutamate-induced neuronal death in the rat hippocampus. We found in cultured rat hippocampal neurons that the exposure to glutamate (100 µM) for 30 min triggers a sustained increase of extracellular ATP levels, which contributes to NMDA receptor (NMDAR)-mediated hippocampal neuronal death through the activation of P2Y1R. We also determined that P2Y1R is involved in excitotoxicity in vivo as the blockade of P2Y1R significantly attenuated rat hippocampal neuronal deat...Continue Reading

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Methods Mentioned

BETA
electrophoresis

Key Resources (RRID) Mentioned

AB_10863775
AB_477523
AB_10122491
AB_2138147
AB_731750
AB_260911
AB_477483
AB_887878
AB_887873
AB_1209349

Software Mentioned

Axiovision
pClamp
MetaFluor
ImageLab
ImageJ
GraphPad
FELASA
Prism
ARRIVE
Neurolucida

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