Ethanol exposure during development reduces GABAergic/glycinergic neuron numbers and lobule volumes in the mouse cerebellar vermis. (6th October 2016)

• Record Type: Journal Article
• Authors: Nirgudkar, Pranita; Taylor, Devin H.; Yanagawa, Yuchio; Valenzuela, C. Fernando
• Is Part Of: Neuroscience letters. Volume 632(2016)
• Page Start: 86
• Page End: 91
• Publication Date: 2016-10-06
• Subjects: Cerebellum -- Vermis -- GABA -- Glycine -- Interneuron -- Ethanol -- Development; Neurology -- Periodicals; Neurology -- Periodicals; Research -- Periodicals; Neurologie -- Périodiques; Neuroanatomie -- Périodiques; Neuropharmacologie -- Périodiques; Neurophysiologie -- Périodiques; Neurology; Periodicals; Electronic journals; 617.48
• DOI: 10.1016/j.neulet.2016.08.039
• Languages: English
• ISSNs: 0304-3940

Abstract

Highlights: Used transgenic mice expressing fluorescent inhibitory neurons. Exposed to ethanol during 2nd and 3rd trimester equivalents. Inhibitory interneurons were reduced in lobule II at postnatal day 16. Purkinje cells were reduced in lobules II, IV–V and IX. Volume of lobules II, IV–V, VI–VII, IX and X was also decreased. 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.