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Alpha7 nicotinic receptor activation inhibits ethanol‐induced mitochondrial dysfunction, cytochrome c release and neurotoxicity in primary rat hippocampal neuronal cultures
Author(s) -
Li Yangxin,
Meyer Edwin M.,
Walker Don W.,
Millard William J.,
He YunJu,
King Michael A.
Publication year - 2002
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.2002.00891.x
Subject(s) - neurotoxicity , nicotinic agonist , neuroprotection , chemistry , mitochondrion , pharmacology , nicotinic antagonist , cytochrome c , receptor , biochemistry , biology , toxicity , organic chemistry
Primary hippocampal neuronal cultures exhibited a concentration‐ and time‐dependent loss of cells when exposed to ethanol (EtOH). EtOH‐induced neurotoxicity was attenuated by 2,4‐dimethoxybenzilidene anabaseine (DMXB) which selectively activates alpha7 nicotinic receptors in a concentration‐dependent manner. We further investigated the mechanisms of the protective effect of DMXB on EtOH‐ induced neurotoxicity. We found that EtOH decreased the mitochondrial membrane potential and released cytochrome c from mitochondria at neurotoxic concentrations. DMXB (3 μ m ) attenuated both of these actions in a manner that was in turn blocked with the nicotinic antagonist methyllyconitine (MLA) 100 n m . Neither DMXB nor MLA alone affected these parameters. These results suggest that the neuroprotection conferred by alpha7 nicotinic receptor activation may be mediated, at least in part, through preventing the decrease in the mitochondrial membrane potential and the increase in the release of cytochrome c caused by EtOH.