title: Ethanol exposure during development reduces GABAergic/glycinergic neuron numbers and lobule volumes in the mouse cerebellar vermis.
abstract: Cerebellar alterations are a hallmark of Fetal Alcohol Spectrum Disorders and are thought to be responsible for deficits in fine motor control, motor learning, balance, and higher cognitive functions. These deficits are, in part, a consequence of dysfunction of cerebellar circuits. Although the effect of developmental ethanol exposure on Purkinje and granule cells has been previously characterized, its actions on other cerebellar neuronal populations are not fully understood. Here, we assessed the impact of repeated ethanol exposure on the number of inhibitory neurons in the cerebellar vermis. We exposed pregnant mice to ethanol in vapor inhalation chambers during gestational days 12-19 and offspring during postnatal days 2-9. We used transgenic mice expressing the fluorescent protein, Venus, in GABAergic/glycinergic neurons. Using unbiased stereology techniques, we detected a reduction in Venus positive neurons in the molecular and granule cell layers of lobule II in the ethanol exposed group at postnatal day 16. In contrast, ethanol produced a more widespread reduction in Purkinje cell numbers that involved lobules II, IV-V and IX. We also found a reduction in the volume of lobules II, IV-V, VI-VII, IX and X in ethanol-exposed pups. These findings indicate that second and third trimester-equivalent ethanol exposure has a greater impact on Purkinje cells than interneurons in the developing cerebellar vermis. The decrease in the volume of most lobules could be a consequence of a reduction in cell numbers, dendritic arborizations, or axonal projections.
authors: Division of Maternal Fetal Medicine, Department of Obstetrics and Gynecology, School of Medicine, University of New Mexico Health Sciences Center, Albuquerque, NM 87131, U.S.A.
authors: Pranita
authors: P
authors: Nirgudkar
authors: Department of Neurosciences, School of Medicine, University of New Mexico Health Sciences Center, Albuquerque, NM 87131, U.S.A.
authors: Devin H
authors: DH
authors: Taylor
authors: Department of Genetic and Behavioral Neuroscience, Gunma University Graduate School of Medicine, Maebashi 371-8511, Japan.
authors: Yuchio
authors: Y
authors: Yanagawa
authors: Department of Neurosciences, School of Medicine, University of New Mexico Health Sciences Center, Albuquerque, NM 87131, U.S.A.. Electronic address: fvalenzuela@salud.unm.edu.
authors: C Fernando
authors: CF
authors: Valenzuela
mesh_terms: D000818:Animals; D002452:Cell Count; D065814:Cerebellar Vermis / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D000431:Ethanol / Q000494:pharmacology*; D005260:Female; D059330:GABAergic Neurons / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D005998:Glycine / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009474:Neurons / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects
chemical_list: D000431:Ethanol; D005998:Glycine
keywords: Cerebellum; Development; Ethanol; GABA; Glycine; Interneuron; Vermis