Glutamate-induced and NMDA receptor-mediated neurodegeneration entails P2Y1 receptor activation
- UNCP Author/Contributor (non-UNCP co-authors, if there are any, appear on document)
- Dr . Ben Bahr, William C. Friday Chair and Professor of Molecular Biology and Biochemistry (Creator)
- Institution
- The University of North Carolina at Pembroke (UNCP )
- Web Site: http://www.uncp.edu/academics/library
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 death upon the systemic administration of kainic acid or upon the intrahippocampal injection of quinolinic acid. This contribution of P2Y1R fades with increasing intensity of excitotoxic conditions, which indicates that P2Y1R is not contributing directly…
Glutamate-induced and NMDA receptor-mediated neurodegeneration entails P2Y1 receptor activation
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Created on 3/27/2018
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Additional Information
- Publication
- Cell Death & Disease Vol. 9, No. 3
- Language: English
- Date: 2018
- Keywords
- NMDA receptor, glutamate-induced neurotoxicity, brain disorder, glutamate, extracellular ATP levels, excitotoxicity, hippocampal, P2Y1R, NMDAR