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Background: Prenatal Alcohol Exposure (PAE) occurs when an expecting mother consumes alcohol at any stages of pregnancy. PAE will lead to children to develop fetal alcohol spectrum disorders (FASDs), which are a group of conditions that can include a wide range of behavior problems, cognitive impairments and distinctive physical features. Oligodendrocyte Precursor cells (OPCs) are glial cells and they’re responsible for generating oligodendrocytes which myelinate neuronal axons to allow proper conduction of action potentials. Decrease myelination in the brain is a prominent feature of PAE both studies in humans and animal models. We hypothesize that third trimester pups exposed to alcohol will show reduced differentiation of mature myelinating oligodendrocytes which is the peak of OPC generation.

Methods: This project utilized a vapor chamber to expose mouse pups to either air (control) or ethanol (experimental) vapor for 4 hours/day under reversed dark-light cycle from postnatal day (P) 4 to P8. On day P3, pups were injected with tamoxifen to induce Cre and label OPCs with YFP reporter to verify OPC presence at the time of alcohol exposure. Pups were either perfused at P8 or kept alive till P30 to study long term effects. Immunohistochemistry and fluorescence microscopy were used to study PAE effects on OPC differentiation into oligodendrocytes in the cortex and corpus callosum. Oligodendrocyte markers OLIG2, MBP, CC1, and Cleaved Caspase 3 (CC3), a cell death marker, were used.

Conclusions: TTAE pups confirmed decreased myelination at P8 based on the expression of MBP, while the number of mature YFP-labeled oligodendrocytes as labeled by CC1 was also decreased at P30 compared to air exposed control mice. CC3 showed that these decreases ware not due to an increase in the death of (OLIG2+) OPCs or oligodendrocytes but showed neuronal cell death. These findings validate that PAE suppresses differentiation of OPCs into oligodendrocytes.

FUNDING: P50 AA022534 Pilot Project 6B, NIAAA; K22 NS092767 & R01 NS121660, NINDS



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