title: 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.
abstract: 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 Mζ (PKMζ), and PKCι/λ 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.
authors.affiliation: Department of Psychology, Center for Development and Behavioral Neuroscience, Binghamton University - State University of New York, Binghamton, NY 13902, USA.
authors.forename: J L
authors.initials: JL
authors.lastname: Santerre
authors.affiliation: Department of Psychology, Center for Development and Behavioral Neuroscience, Binghamton University - State University of New York, Binghamton, NY 13902, USA.
authors.forename: J A
authors.initials: JA
authors.lastname: Rogow
authors.affiliation: Department of Psychology, Center for Development and Behavioral Neuroscience, Binghamton University - State University of New York, Binghamton, NY 13902, USA.
authors.forename: E B
authors.initials: EB
authors.lastname: Kolitz
authors.affiliation: Department of Psychology, Center for Development and Behavioral Neuroscience, Binghamton University - State University of New York, Binghamton, NY 13902, USA.
authors.forename: R
authors.initials: R
authors.lastname: Pal
authors.affiliation: Department of Psychology, Center for Development and Behavioral Neuroscience, Binghamton University - State University of New York, Binghamton, NY 13902, USA.
authors.forename: J D
authors.initials: JD
authors.lastname: Landin
authors.affiliation: Department of Psychology, Center for Development and Behavioral Neuroscience, Binghamton University - State University of New York, Binghamton, NY 13902, USA.
authors.forename: E D
authors.initials: ED
authors.lastname: Gigante
authors.affiliation: Department of Psychology, Center for Development and Behavioral Neuroscience, Binghamton University - State University of New York, Binghamton, NY 13902, USA. Electronic address: dwerner@binghamton.edu.
authors.forename: D F
authors.initials: DF
authors.lastname: Werner
mesh_terms: D000375:Aging / Q000378:metabolism; D000818:Animals; D002492:Central Nervous System Depressants / Q000494:pharmacology*; D002540:Cerebral Cortex / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism; D064550:Death-Associated Protein Kinases / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D000431:Ethanol / Q000494:pharmacology*; D006624:Hippocampus / Q000187:drug effects* / Q000254:growth & development / Q000378:metabolism; D008297:Male; D010766:Phosphorylation; D011493:Protein Kinase C / Q000378:metabolism; D051745:Protein Kinase C-delta / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D018091:Receptors, AMPA / Q000378:metabolism*; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism
chemical_list: D002492:Central Nervous System Depressants; D018091:Receptors, AMPA; D000431:Ethanol; D064550:Death-Associated Protein Kinases; D011493:Protein Kinase C; D051745:Protein Kinase C-delta; C504730:protein kinase M zeta, rat; C104722:glutamate receptor ionotropic, AMPA 2
keywords: AMPA receptors GluA2 subunits; PKCι/λ; PKMζ; adolescence; ethanol; protein kinase C (PKC)