title: Moderate fetal alcohol exposure impairs the neurogenic response to an enriched environment in adult mice.
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 approximately 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.
authors.affiliation: Department of Neurosciences, University of New Mexico, Albuquerque, NM 87131-0001, USA.
authors.forename: Irene Y
authors.initials: IY
authors.lastname: Choi
authors.forename: Andrea M
authors.initials: AM
authors.lastname: Allan
authors.forename: Lee Anna
authors.initials: LA
authors.lastname: Cunningham
mesh_terms: D000818:Animals; D001973:Bromodeoxyuridine / Q000494:pharmacology; D018891:Dentate Gyrus / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D004195:Disease Models, Animal; D004779:Environment Design; D000431:Ethanol / Q000097:blood / Q000633:toxicity*; D005260:Female; D063647:Fetal Alcohol Spectrum Disorders / Q000378:metabolism; D047109:Fetal Development / Q000187:drug effects / Q000502:physiology; D005333:Fetus / Q000187:drug effects* / Q000502:physiology; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D006799:Housing, Animal / Q000592:standards; D007150:Immunohistochemistry; D008431:Maternal-Fetal Exchange; D051379:Mice; D009473:Neuronal Plasticity / Q000187:drug effects* / Q000502:physiology; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects
chemical_list: D000431:Ethanol; D001973:Bromodeoxyuridine