THE IMPACT OF NEONATAL ALCOHOL EXPOSURE AND VOLUNTARY EXERCISE ON CHOLINERGIC FIBER LENGTH AND CG2 VOLUME IN THE RAT MEDIAL PREFRONTAL CORTEX

Abstract

Prenatal alcohol exposure is known to cause chronic behavioral impairment and neurocognitive deficits diagnosed as Fetal Alcohol Spectrum Disorders (FASD). With a prevalence of one in every twenty children affected by prenatal alcohol exposure in the United States, FASD remains a serious public health concern. This study uses a rodent model of FASD to investigate the effects of third trimesterequivalent alcohol exposure and adolescent exercise intervention on the underexplored cortical-projecting pathway of the central cholinergic system, the nucleus basalis of Meynert (NBM)-cortical pathway. Recent literature has found that neonatal choline supplementation following prenatal alcohol exposure may ameliorate some alcoholinduced cognitive deficits, but the structural basis of these functional changes has not yet been investigated. Therefore, the current study examines cholinergic fiber length along the NBM-cortical cholinergic pathway and Cg2 volume of the medial prefrontal cortex (mPFC) in our experimental paradigm. Alcohol exposed (AE) male Long- Evans pups received ethanol in a binge-like manner (5.25 g/kg/day) twice a day during postnatal day (PD) 4-9. Control groups consisted of sham-intubated (SI) and suckle control (SC) rats. Pups were weaned on PD23 and socially housed in same-sex groups of three. Wheel running (WR) rats had 24-hour voluntary access to a running wheel from PD30-72. All animals were sacrificed on PD72 and forebrain tissue was collected and histochemically stained via a Hedreen and Bacon modified Karnovsky- Roots method to visualize acetylcholinesterase (AChE)-positive fibers in Cg2. Overall, there was no significant effect of postnatal treatment or behavioral intervention on cholinergic fiber length or Cg2 volume in adulthood. No significant interactions were observed. These data indicate that cholinergic axons are innervating their mPFC target region in adulthood. Future investigation is necessary to elucidate cellular cholinergic mechanisms affected by neonatal alcohol exposure that may be contributing to the observed PFC-dependent cognitive deficits characteristic of FASD.