Effects of neonatal alcohol exposure on oligodendrocyte-lineage cell quantity in the rat corpus callosum
Date
2022
Authors
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Publisher
University of Delaware
Abstract
As many as 1 in 9 live births in the United States have been exposed to alcohol prenatally in levels sufficient to produce the lasting physical, behavioral, and cognitive deficits known as Fetal Alcohol Spectrum Disorders (FASD). While first trimester exposure may result in the most distinct and easily recognizable physical dysmorphologies, late-term exposures may result in behavioral and cognitive symptoms such as deficits in executive function that are more difficult to diagnose. One brain structure associated with these functions that is also known to be affected by prenatal alcohol exposure is the corpus callosum (CC), the heavily myelinated white matter tract that connects the two hemispheres of the brain. It is also known that FASD symptoms are sexually dimorphic, although the mechanisms underlying sex effects remain understudied. In addition to clinical populations, these effects have been observed in preclinical animal studies, which allow researchers to ask specific questions about the neurobiological underpinnings of structural changes in a tightly regulated experimental environment that must be answered to understand the ways in which alcohol acts as a teratogen. ☐ This study utilizes a rat model of third trimester alcohol exposure to assess its effects on CC development. We tested the hypothesis that teratogenic alcohol exposure reduces oligodendrocyte precursor cell (OPC) and mature oligodendrocyte (OL) populations in both sexes at postnatal day (PD) 10 and PD 15. A total of 79 Long-Evans rats were reared, with approximately half receiving binge-like alcohol exposure (5.25 g/kg/day) during the PD 4-9 brain growth spurt and half receiving sham intubation with no liquid administration. Brain tissue from cohort 1 was collected for analysis at PD 10, and cohort 2 brain tissue was collected at PD 15. ☐ A teratogenic effect of alcohol on OLs was found in a sexually dimorphic manner. Specifically, OLs were reduced in alcohol-exposed females at PD 10 and in both sexes at PD 15, while OPCs were unaffected in all groups. Additionally, a general increase in OL quantity from PD 10 to PD 15 was observed in females only. This study represents an important first step in elucidating the mechanisms of FASD- induced CC damage. The Klintsova Lab intends to build upon these findings by replicating this analysis on earlier and later time points and pairing these data with analysis of myelin basic protein expression, individual myelin sheath thickness via electron microscopy, and CC macrostructure via neuroimaging.
Description
Keywords
Corpus callosum, Fetal alcohol spectrum disorders, Immunohistochemistry, Oligodendrocyte, Oligodendrocyte precursor cell, Sex differences