Adolescent binge alcohol exposure induces long-lasting partial activation of microglia.
Accumulating evidence indicates that the adolescent hippocampus is highly susceptible to alcohol-induced structural damage and behavioral deficits. Microglia are vitally important brain constituents needed to support and maintain proper neural function; however, alcohol's effects on microglia have only recently gained attention. The microglial response to alcohol during adolescence has yet to be studied; therefore, we examined hippocampal microglial activation in an adolescence binge alcohol exposure model. Adolescent male Sprague-Dawley rats were administered ethanol 3 times/day for 4 days and were sacrificed 2, 7, and 30 days later. Bromo-deoxy-Uridine was injected 2 days after ethanol exposure to label dividing cells. Microglia morphology was scored using the microglia marker Iba-1, while the extent of microglial activation was examined with ED-1, major histocompatibility complex-II (MHC-II), and tumor necrosis factor (TNF)-α expression. Ethanol induced significant morphological change in hippocampal microglia, consistent with activation. In addition, ethanol increased the number of BrdU+ cells throughout all regions of the hippocampus 2 days after the last dose. Confocal microscopy showed that the proliferating BrdU+ cells in each region were Iba-1+ microglia. Importantly, newly born microglia survived and retained their morphological characteristics 30 days after ethanol exposure. Ethanol did not alter hippocampal ED-1, MHC-II, or TNF-α expression, suggesting that a single period of binge ethanol exposure does not induce a full microglial-driven neuroinflammatory response. These results establish that ethanol triggers partial microglial activation in the adolescent hippocampus that persists through early adulthood, suggesting that alcohol exposure during this unique developmental time period has long-lasting consequences.
Department of Pharmaceutical Sciences, The University of Kentucky, Lexington, KY 40536, USA.
Justin A
JA
McClain
Stephanie A
SA
Morris
M Ayumi
MA
Deeny
S Alex
SA
Marshall
Dayna M
DM
Hayes
Zachary M
ZM
Kiser
Kimberly
K
Nixon
D000428:Alcohol Drinking / Q000276:immunology*; D000818:Animals; D048430:Cell Shape / Q000187:drug effects; D004797:Enzyme-Linked Immunosorbent Assay; D000431:Ethanol / Q000008:administration & dosage*; D006624:Hippocampus / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D007150:Immunohistochemistry; D008297:Male; D017628:Microglia / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D014409:Tumor Necrosis Factor-alpha; D000431:Ethanol
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