ETHANOL DOSE-DEPENDENTLY ELICITS OPPOSING REGULATORY EFFECTS ON HIPPOCAMPAL AMPA RECEPTOR GLUA2 SUBUNITS THROUGH A ZETA INHIBITORY PEPTIDE-SENSITIVE KINASE IN ADOLESCENT AND ADULT SPRAGUE-DAWLEY RATS

被引：9

作者：

Santerre, J. L. ^{[1
]}

Rogow, J. A. ^{[1
]}

Kolitz, E. B. ^{[1
]}

Pal, R. ^{[1
]}

Landin, J. D. ^{[1
]}

Gigante, E. D. ^{[1
]}

Werner, F. ^{[1
]}

机构：

[1] SUNY Binghamton, Dept Psychol, Ctr Dev & Behav Neurosci, Binghamton, NY 13902 USA

来源：

NEUROSCIENCE | 2014年 / 280卷

关键词：

adolescence; ethanol; protein kinase C (PKC); PKW zeta; PKC iota/lambda; AMPA receptors GluA2 subunits; LONG-TERM POTENTIATION; PKM-ZETA; SYNAPTIC PLASTICITY; MEMORY; PHOSPHORYLATION; EXPOSURE; DOMAIN; GLUR2; MAINTENANCE; TRAFFICKING;

D O I：

10.1016/j.neuroscience.2014.09.003

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

AMPA receptor GluA2 subunits are strongly implicated in cognition, and prior work suggests that these subunits may be regulated by atypical protein kinase C (aPKC) isoforms. The present study assessed whether hippocampal and cortical AMPA receptor GluA2 subunit regulation may be an underlying factor in known age-related differences to cognitive-impairing doses of ethanol, and if aPKC isoforms modulate such responses. Hippocampal AMPA receptor GluA2 subunit, protein kinase M zeta (PKM zeta), and PKC iota/lambda expression were elevated during adolescence compared to adults. 1 h following a low-dose (1.0-g/kg) ethanol exposure, hippocampal AMPA receptor GluA2 subunit serine 880 phosphorylation was decreased in adolescents, but was increased in adults. Age-dependent changes in GluA2 subunit phosphorylation were paralleled by alterations in aPKC isoforms, and zeta inhibitory peptide (ZIP) administration prevented ethanol-induced increases in both in adults. Ethanol-induced changes in GluA2 subunit phosphorylation were associated with delayed regulation in synaptosomal GluA2 subunit expression 24 h later. A higher ethanol dose (3.5-g/kg) failed to elicit changes in most measures in the hippocampus at either age. Similar to the hippocampus, analysis of cerebral cortical tissue also revealed age-related declines. However, no demonstrable effects were found following a low-dose ethanol exposure at either age. High-dose ethanol exposure reduced adolescent GluA2 subunit phosphorylation and aPKC isoform expression that were again accompanied by delayed reductions in synaptosomal GluA2 subunit expression. Together, these results suggest that GluA2-containing AMPA receptor modulation by aPKC isoforms is age-, region- and dose-dependently regulated, and may potentially be involved in developmentally regulated ethanol-induced cognitive impairment and other ethanol behaviors. (C) 2014 IBRO. Published by Elsevier Ltd. All rights reserved.

引用

页码：50 / 59

页数：10

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