title: Fate analysis of adult hippocampal progenitors in a murine model of fetal alcohol spectrum disorder (FASD).
abstract: Prenatal alcohol exposure can lead to fetal alcohol spectrum disorder (FASD) and associated behavioral impairments that may be linked to disruptions in adult hippocampal neurogenesis. Social and physical enrichment has been proposed as a potential therapeutic approach toward reversing behavioral deficits associated with FASD and is also a potent stimulator of adult hippocampal neurogenesis. In the present study, we utilized a genetic fate mapping approach in nestin-CreER(T2)/YFP bitransgenic mice to identify the stage-specific impact of prenatal alcohol exposure on the stepwise maturation of adult hippocampal progenitors. Using a limited alcohol access "drinking-in-the-dark" model of FASD, we confirm previous findings that moderate prenatal alcohol exposure has no effect on adult neurogenesis under standard housing conditions, but abolishes the neurogenic response to enriched environment (EE). Furthermore, we demonstrate that this effect is primarily due to failed EE-mediated survival of postmitotic neurons. Finally, we demonstrate that the neurogenic deficit is associated with impaired spatial pattern recognition, as demonstrated by delayed learning of FASD-EE mice in an A-B contextual discrimination task. These results identify a potential maturational stage-specific mechanism(s) underlying impaired neurogenic function in a preclinical model of FASD, and provide a basis for testing regulatory pathways in this model through conditional and inducible manipulation of gene expression in the adult hippocampal progenitor population.
authors.affiliation: Department of Neurosciences, University of New Mexico School of Medicine, Albuquerque, New Mexico, United States of America.
authors.forename: Kenta
authors.initials: K
authors.lastname: Kajimoto
authors.forename: Andrea
authors.initials: A
authors.lastname: Allan
authors.forename: Lee Anna
authors.initials: LA
authors.lastname: Cunningham
mesh_terms: D000328:Adult; D000428:Alcohol Drinking / Q000009:adverse effects; D000818:Animals; D002492:Central Nervous System Depressants / Q000633:toxicity; D004195:Disease Models, Animal; D000431:Ethanol / Q000633:toxicity*; D005260:Female; D063647:Fetal Alcohol Spectrum Disorders / Q000209:etiology* / Q000235:genetics; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D007859:Learning Disabilities / Q000209:etiology / Q000235:genetics; D008164:Luminescent Proteins / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D018613:Microscopy, Confocal; D064231:Nestin / Q000235:genetics / Q000378:metabolism; D055495:Neurogenesis / Q000187:drug effects / Q000235:genetics; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000139:chemically induced* / Q000235:genetics; D013234:Stem Cells / Q000187:drug effects* / Q000378:metabolism
chemical_list: D002492:Central Nervous System Depressants; D008164:Luminescent Proteins; D064231:Nestin; D000431:Ethanol
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