This work is supported by Alcohol Research Training in Neurosciences NIAAA T32 AA014127, NIAAA 1R21 AA014165 (LAC), and by the U.S. Department of Army Awards #DAMD 17-01-1-0608 (AMA). Images in this paper were generated in the UNM Cancer Center Fluorescence Microscopy Facility which received support from NCRR 1 S10 RR14668, NSF MCB9982161, NCRR P20 RR11830, NCI R24 CA88339, NCRR S10 RR19287, NCRR S10 RR016918, the University of New Mexico Health Sciences Center, and the University of New Mexico Cancer Center.
Moderate Fetal Alcohol Exposure Impairs the Neurogenic Response to an Enriched Environment in Adult Mice
Version of Record online: 3 MAY 2006
Alcoholism: Clinical and Experimental Research
Volume 29, Issue 11, pages 2053–2062, November 2005
How to Cite
Choi, I. Y., Allan, A. M. and Cunningham, L. A. (2005), Moderate Fetal Alcohol Exposure Impairs the Neurogenic Response to an Enriched Environment in Adult Mice. Alcoholism: Clinical and Experimental Research, 29: 2053–2062. doi: 10.1097/01.alc.0000187037.02670.59
- Issue online: 3 MAY 2006
- Version of Record online: 3 MAY 2006
- Received for publication May 2, 2005; accepted August 10, 2005.
- Adult Neurogenesis;
- Voluntary Drinking
Abstract: Background: Prenatal ethanol exposure results in a spectrum of cognitive and behavioral deficits and affects an estimated thirteen percent of children born in the United States. The basis of prenatal ethanol-induced impairment of brain function has been widely studied in animal models, where significant changes in the physiological and structural plasticity of hippocampal function have been documented. Here, we explored the possibility that exposure to moderate levels of alcohol in utero might also result in long-lasting impairment of adult hippocampal neurogenesis, a novel form of plasticity that occurs throughout adulthood.
Methods: Female mice were trained to voluntarily consume 10% EtOH throughout pregnancy using the two-bottle choice paradigm, which results in moderate blood alcohol levels of ∼121 mg/dl, as previously described (Allan et al., 2003). Offspring were exposed to standard or enriched living conditions for 8–12 weeks post-weaning. BrdU was administered at 50 mg/kg for 12 consecutive days. Mice in each housing condition were sacrificed at either 24 hrs or four weeks following the final BrdU injection, and BrdU+ cells within the dentate gyrus were evaluated using immuno-histochemical methods.
Results: Neither fetal alcohol exposure (FAE) nor enriched environment affected the number of proliferating progenitors within the subgranular zone (SGZ) of the dentate gyrus. However, FAE severely impaired the neurogenic response to enriched environment. Control mice housed in enriched environment displayed a two-fold increase in hippocampal neurogenesis, whereas FAE mice responded to enriched environment with neither enhanced progenitor survival nor enhanced neuronal differentiation.
Conclusions: These observations indicate that moderate FAE results in a long-term, persistent defect in neurogenic responses to behavioral challenge.