Please use this identifier to cite or link to this item: http://repositorio.unicamp.br/jspui/handle/REPOSIP/100867
Type: Artigo de evento
Title: Glutamate Excitotoxicity And Neuronal Energy Metabolism
Author: Nicholls D.G.
Budd S.L.
Castilho R.F.
Ward M.W.
Abstract: The bioenergetic properties of the in situ mitochondria play a central role in controlling the susceptibility of neurons to acute or chronic neurodegenerative stress. The mitochondrial membrane potential, Δψ(m), is the parameter that controls three interrelated mitochondrial functions of great relevance to neuronal survival: namely, ATP synthesis, Ca2+ accumulation, and superoxide generation. The in vitro model we study is the rat cerebellar granule cell in primary culture and its susceptibility to NMDA receptor-mediated necrosis, which is preceded by a delayed failure of cytoplasmic Ca2+ homeostasis ('delayed Ca2+ deregulation,' DCD). DCD is not caused by a failure of mitochondrial ATP synthesis since it also occurs in cells maintained purely by glycolysis. The in situ mitochondria maintain a Δψ(m), sufficient for ATP synthesis throughout the exposure of the cells to glutamate until DCD occurs. Even at that stage it appears that mitochondrial depolarization may be an effect of DCD rather than a primary cause. This somewhat unorthodox view resolves a number of apparent paradoxes, such as observations of enhanced superoxide generation by in situ mitochondria during excitotoxic exposure, since isolated mitochondria generate superoxide only under conditions of high Δψ(m). Mitochondrial depolarization by selective inhibitors that do not deplete cellular ATP is acutely neuroprotective.
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Rights: fechado
Identifier DOI: 
Address: http://www.scopus.com/inward/record.url?eid=2-s2.0-0033389135&partnerID=40&md5=a0c05bf634972d1cef430aa777f5ba01
Date Issue: 1999
Appears in Collections:Unicamp - Artigos e Outros Documentos

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