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KMID : 1161520120160030190
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Animal Cells and Systems
2012 Volume.16 No. 3 p.190 ~ p.197
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Alcohol exposure induces depression-like behavior by decreasing hippocampal neuronal proliferation through inhibition of the BDNF-ERK pathway in gerbils
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Kim Ji-Eun
Ji Eun-Sang
Seo Jin-Hee
Lee Moon-Hyoung
Cho Se-Hyung
Pak Young-Mi Kim
Seo Tae-Beom
Kim Chang-Ju
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Abstract
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Depression is one of the most prevalent diseases of alcohol abuse. Brain-derived neurotrophic factor (BDNF) plays a critical role in cell survival in the hippocampus. Phosphorylation of extracellular signal-regulated kinase 1/2 (p-ERK1/2) is induced by BDNF, and it regulates cell proliferation and differentiation in the brain. We investigated the effects of alcohol intake on depression-like behavior, cell proliferation, expressions of BDNF and its downstream molecules in the hippocampus using Mongolian gerbils. The gerbils were divided into four groups: control group, 0.5 g/kg alcohol-treated group, 1 g/kg alcohol-treated group, 2 g/kg alcohol-treated group. Each dose of alcohol was orally administered for 3 weeks. The present results demonstrated that alcohol intake induced depression-like behavior. Both 5-hydroxytryptamine synthesis and its synthesizing enzyme tryptophan hydroxylase expression in the dorsal raphe and cell proliferation in the hippocampal dentate gyrus were decreased by alcohol intake. Alcohol intake suppressed BDNF expression, and resulted in the decrease of its downstream molecules, pERK1/2 and Bcl-2, in the hippocampus. We showed that alcohol intake may lead to a depressed-like state with reduced hippocampal cell proliferation through inhibition of the BDNF-ERK signaling pathway.
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KEYWORD
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alcohol, depression, cell proliferation, brain-derived neurotrophic factor, extracellular signal-regulated kinase 1/2
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