title: Altered adult hippocampal neuronal maturation in a rat model of fetal alcohol syndrome.
abstract: Exposure to ethanol during pregnancy can be devastating to the developing nervous system, leading to significant central nervous system dysfunction. The hippocampus, one of the two brain regions where neurogenesis persists into adulthood, is particularly sensitive to the teratogenic effects of ethanol. In the present study, we tested a rat model of fetal alcohol syndrome (FAS) with ethanol administered via gavage throughout all three trimester equivalents. Subsequently, we assessed cell proliferation, as well as neuronal survival, and differentiation in the dentate gyrus of the hippocampus of adolescent (35 days old), young adult (60 days old) and adult (90 days old) Sprague-Dawley rats. Using both extrinsic (bromodeoxyuridine) and intrinsic (Ki-67) markers, we observed no significant alterations in cell proliferation and survival in ethanol-exposed animals when compared with their pair-fed and ad libitum controls. However, we detected a significant increase in the number of new immature neurons in animals that were exposed to ethanol throughout all three trimester equivalents. This result might reflect a compensatory mechanism to counteract the deleterious effects of prenatal ethanol exposure or an ethanol-induced arrest of the neurogenic process at the early neuronal maturation stages. Taken together these results indicate that exposure to ethanol during the period of brain development causes a long-lasting dysregulation of the neurogenic process, a mechanism that might contribute, at least in part, to the hippocampal deficits that have been reported in rodent models of FAS.
authors.affiliation: Division of Medical Sciences, Island Medical Program, University of Victoria, Victoria, British Columbia, Canada.
authors.forename: Joana
authors.initials: J
authors.lastname: Gil-Mohapel
authors.forename: Fanny
authors.initials: F
authors.lastname: Boehme
authors.forename: Anna
authors.initials: A
authors.lastname: Patten
authors.forename: Adrian
authors.initials: A
authors.lastname: Cox
authors.forename: Leah
authors.initials: L
authors.lastname: Kainer
authors.forename: Erica
authors.initials: E
authors.lastname: Giles
authors.forename: Patricia S
authors.initials: PS
authors.lastname: Brocardo
authors.forename: Brian R
authors.initials: BR
authors.lastname: Christie
mesh_terms: D000367:Age Factors; D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D051792:Basic Helix-Loop-Helix Proteins / Q000378:metabolism; D001835:Body Weight; D002470:Cell Survival; D004195:Disease Models, Animal; D004435:Eating / Q000502:physiology; D000431:Ethanol / Q000009:adverse effects / Q000097:blood; D005260:Female; D063647:Fetal Alcohol Spectrum Disorders / Q000473:pathology* / Q000503:physiopathology*; D006624:Hippocampus / Q000254:growth & development* / Q000473:pathology*; D019394:Ki-67 Antigen / Q000378:metabolism; D008297:Male; D009474:Neurons / Q000502:physiology*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000503:physiopathology; D051381:Rats
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D000431:Ethanol; D019394:Ki-67 Antigen; C490555:Neurod1 protein, rat