title: Behavioral deficits induced by third-trimester equivalent alcohol exposure in male C57BL/6J mice are not associated with reduced adult hippocampal neurogenesis but are still rescued with voluntary exercise.
abstract: Prenatal alcohol exposure can produce permanent alterations in brain structure and profound behavioral deficits. Mouse models can help discover mechanisms and identify potentially useful interventions. This study examined long-term influences of either a single or repeated alcohol exposure during the third-trimester equivalent on survival of new neurons in the hippocampus, behavioral performance on the Passive avoidance and Rotarod tasks, and the potential role of exercise as a therapeutic intervention. C57BL/6J male mice received either saline or 5g/kg ethanol split into two s.c. injections, two hours apart, on postnatal day (PD)7 (Experiment 1) or on PD5, 7 and 9 (Experiment 2). All mice were weaned on PD21 and received either a running wheel or remained sedentary from PD35-PD80/81. From PD36-45, mice received i.p. injections of 50mg/kg bromodeoxyuridine (BrdU) to label dividing cells. Behavioral testing occurred between PD72-79. Number of surviving BrdU+ cells and immature neurons (doublecortin; DCX+) was measured at PD80-81. Alcohol did not affect number of BrdU+ or DCX+ cells in either experiment. Running significantly increased number of BrdU+ and DCX+ cells in both treatment groups. Alcohol-induced deficits on Rotarod performance and acquisition of the Passive avoidance task (Day 1) were evident only in Experiment 2 and running rescued these deficits. These data suggest neonatal alcohol exposure does not result in long-term impairments in adult hippocampal neurogenesis in the mouse model. Three doses of ethanol were necessary to induce behavioral deficits. Finally, the mechanisms by which exercise ameliorated the neonatal alcohol induced behavioral deficits remain unknown.
authors: Department of Psychology, The Beckman Institute, 405 N Mathews Ave, University of Illinois at Urbana-Champaign, Urbana, IL, 61801, USA. Electronic address: gillianh@illinois.edu.
authors: G F
authors: GF
authors: Hamilton
authors: Department of Psychology, The Beckman Institute, 405 N Mathews Ave, University of Illinois at Urbana-Champaign, Urbana, IL, 61801, USA.
authors: P J
authors: PJ
authors: Bucko
authors: Department of Psychology, The Beckman Institute, 405 N Mathews Ave, University of Illinois at Urbana-Champaign, Urbana, IL, 61801, USA.
authors: D S
authors: DS
authors: Miller
authors: Department of Psychology, The Beckman Institute, 405 N Mathews Ave, University of Illinois at Urbana-Champaign, Urbana, IL, 61801, USA.
authors: R S
authors: RS
authors: DeAngelis
authors: Department of Psychology, The Beckman Institute, 405 N Mathews Ave, University of Illinois at Urbana-Champaign, Urbana, IL, 61801, USA.
authors: C P
authors: CP
authors: Krebs
authors: Department of Psychology, The Beckman Institute, 405 N Mathews Ave, University of Illinois at Urbana-Champaign, Urbana, IL, 61801, USA.
authors: J S
authors: JS
authors: Rhodes
mesh_terms: D000818:Animals; D001522:Behavior, Animal; D002470:Cell Survival / Q000187:drug effects; D000089662:Doublecortin Protein; D000431:Ethanol / Q000494:pharmacology*; D006624:Hippocampus / Q000187:drug effects* / Q000502:physiology; D008297:Male; D008810:Mice, Inbred C57BL; D009043:Motor Activity / Q000187:drug effects*; D055495:Neurogenesis / Q000187:drug effects* / Q000502:physiology; D009474:Neurons / Q000187:drug effects; D010805:Physical Conditioning, Animal / Q000502:physiology
chemical_list: C000714847:Dcx protein, mouse; D000089662:Doublecortin Protein; D000431:Ethanol
keywords: Bromodeoxyuridine; Fetal alcohol spectrum disorders; Hippocampus; Passive avoidance; Running