title: Ectopic hippocampal neurogenesis in adolescent male rats following alcohol dependence.
abstract: The adolescent hippocampus is highly vulnerable to alcohol-induced damage, which could contribute to their increased susceptibility to alcohol use disorder. Altered adult hippocampal neurogenesis represents one potential mechanism by which alcohol (ethanol) affects hippocampal function. Based on the vulnerability of the adolescent hippocampus to alcohol-induced damage, and prior reports of long-term alcohol-induced effects on adult neurogenesis, we predicted adverse effects on adult neurogenesis in the adolescent brain following abstinence from alcohol dependence. Thus, we examined neurogenesis in adolescent male rats during abstinence following a 4-day binge model of alcohol dependence. Bromodeoxyuridine and Ki67 immunohistochemistry revealed a 2.2-fold increase in subgranular zone cell proliferation after 7 days of abstinence. Increased proliferation was followed by a 75% increase in doublecortin expression and a 56% increase in surviving bromodeoxyuridine-labeled cells 14 and 35 days post-ethanol exposure, respectively. The majority of newborn cells in ethanol and control groups co-localized with NeuN, indicating a neuronal phenotype and therefore a 1.6-fold increase in hippocampal neurogenesis during abstinence. Although these results mirror the magnitude of reactive neurogenesis described in adult rat studies, ectopic bromodeoxyuridine and doublecortin positive cells were detected in the molecular layer and hilus of adolescent rats displaying severe withdrawal symptoms, an effect that has not been described in adults. The presence of ectopic neuroblasts suggests that a potential defect exists in the functional incorporation of new neurons into the existing hippocampal circuitry for a subset of rats. Age-related differences in functional incorporation could contribute to the increased vulnerability of the adolescent hippocampus to ethanol.
authors.affiliation: Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, Lexington, KY, USA.
authors.forename: Justin A
authors.initials: JA
authors.lastname: McClain
authors.forename: Stephanie A
authors.initials: SA
authors.lastname: Morris
authors.forename: S Alexander
authors.initials: SA
authors.lastname: Marshall
authors.forename: Kimberly
authors.initials: K
authors.lastname: Nixon
mesh_terms: D000437:Alcoholism / Q000503:physiopathology*; D000818:Animals; D002492:Central Nervous System Depressants / Q000494:pharmacology*; D004195:Disease Models, Animal; D000089662:Doublecortin Protein; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D000431:Ethanol / Q000494:pharmacology*; D006624:Hippocampus / Q000187:drug effects*; D006801:Humans; D008297:Male; D055495:Neurogenesis / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013375:Substance Withdrawal Syndrome / Q000503:physiopathology*
chemical_list: D002492:Central Nervous System Depressants; C000714848:Dcx protein, rat; D000089662:Doublecortin Protein; D000431:Ethanol
keywords: Alcoholism; ethanol; withdrawal