Investigation of Cell Type-Specific Loss in the Nucleus Reuniens of the Midline Thalamus following Single-Day Alcohol Exposure in a Rodent Model of FASD

Date
2023-05
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University of Delaware
Abstract
Fetal Alcohol Spectrum Disorders (FASDs) is an umbrella term used to describe multiple developmental disorders stemming from the prenatal alcohol exposure that are manifested by deficits in growth development, cognitive impairments, and physical abnormalities. 2-5% of live births in the US are affected by FASD and result in lower brain volume, brain anomalies, and behavioral deficits including impaired executive function. Executive function (EF) defines a set of cognitive controls that aid in the formation of goal-directed movements and regulating self-control; EF has been shown to relate to medial prefrontal cortex (mPFC) and hippocampus (HPC) activity. An intermediary structure, the nucleus reuniens (Re) of the midline thalamus, facilitates communication between the mPFC and HPC and is known to be damaged by prenatal alcohol exposure. A damaged Re is known to produce deficits in EF due to inefficient communication in the mPFC-Re-HPC circuit. This study employed a rodent model of third-trimester single-day binge alcohol exposure (AE) to evaluate neuroanatomical effects of neonatal alcohol exposure. Specifically, we examined moderate (3g/kg/day), and high (5/25g/kg/day) doses of ethanol compared to a sham-intubated control group. In conjunction with histological immunofluorescence staining, this study measured the numbers of specific cell populations in Re to assess levels of cell loss at 12hrs after AE. Specifically, we estimated the total number of neurons and oligodendrocytes in Re by labelling these cells with specific antibody markers NeuN (neuronal marker) and CC1 (marker for mature oligodendrocytes). No significant effect of postnatal treatment was found on neuron and oligodendrocyte populations in Re which indicates that cell loss might occur later than 12 hours following AE, as found in studies examining apoptotic-cell expression at 5 and 24 hours (Phanithi, et al., 2000). Additionally, no significant effect of alcohol exposure on reuniens volume was found, indicating that reuniens volume was not compromised within 12 hours of AE. This study aids in our understanding of FASD and adds to the general portrait of the effects of ethanol on the brain and Re
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