Behavioral Therapy to Ameliorate the Effects of Neonatal Alcohol Exposure on Dendritic Organization of Pyramidal Neurons in the Rodent mPFC

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University of Delaware
During the third trimester of pregnancy in humans, a brain goes through the phase of rapid growth known as “brain growth spurt.” A comparable event in brain development occurs in the first ten postnatal days of a rat’s life. Third trimester alcohol exposure (or its equivalent) results in impaired cognition in adulthood and permanent structural changes in the brain, including the prefrontal cortex. The present study uses a rat model to examine the effect of neonatal alcohol exposure on dendritic morphology of pyramidal neurons in Layer III of the medial prefrontal cortex (mPFC), one of the last brain areas to develop in both humans and rats. Specifically, the density and phenotype of dendritic spines were analyzed. The present study also explores the impact of physical activity (wheel running WR) on dendritic morphology of mPFC neurons. Rat pups were randomly assigned to three groups: intubated with alcohol (5.25 g/kg/day; AE), sham intubated (SI), or suckle controls (SC) on PD 4–9. In order to study the effect of voluntary exercise, animals were placed in cages where they had 24-hour access to wheels during PD30-42. On the final day treatment, rats were anesthetized and perfused with 0.9% saline. Brains were subsequently processed for Golgi-Cox staining. Spine density and spine phenotypes were analyzed for basilar dendrites of Layer III mPFC neurons. The present study found that neonatal exposure to alcohol results in reduced spine density in both proximal and distal branches of basilar dendrites. This outcome was ameliorated following exposure to WR. In contrast, no differences in spine phenotype ratios were observed, but it was found that that regardless of housing and postnatal treatment, proximal branches had significantly more mature spines than distal branches.
behavioral therapy, neonatal alcohol exposure, medial prefrontal cortex, dendritic morphology