Examining the Effects of Third Trimester Alcohol Exposure and Behavioral Super Intervention in a Rodent Model of FASDs


  • Isabella De Guzman, Neuroscience, Fordham University

Faculty Mentor(s)

  • Anna Klintsova, Psychological and Brain Sciences, University of Delaware


Alcohol exposure during pregnancy can lead to Fetal Alcohol Spectrum Disorders (FASD). Indications of FASDs include behavioral and cognitive deficits and impaired executive functioning, which relies on the coordinated activity of the medial prefrontal cortex (mPFC) and the hippocampus (HPC) via the thalamic nucleus reuniens (Re). Vulnerability of brain structure to teratogenic effects of alcohol depends on the timing of alcohol exposure during development. Later-developing structures (including mPFC and HPC) are known to be damaged by alcohol during the brain growth spurt (third trimester of human pregnancy). Previous studies show that alcohol exposure during that period decreases the amount of axonal material that originates from the mPFC in the Re in female animals. The current study aims to identify if behavioral intervention can reverse these deficits to axon growth. We employed a rodent model of third trimester alcohol exposure where rat pups were given a binge-like dose of alcohol (5.25g/kg/day, twice a day, separated by two hours) during postnatal days 4-9. Sham intubated pups served as procedural controls. Half of the rats were either assigned to the intervention group consisting of 12 days of wheel running (WR) followed by 30 days of environmental complexity housing (EC) or control social housing (SH). All rats were stereotaxically injected with anterograde viral tracers (AAV5-CAG-tdTomato or AAV5-CAG-GFP) into the left mPFC and HPC between WR and EC to label axon projections within Re. All rats were sacrificed and brains fixed via intracardial perfusion immediately following the end of the intervention period. Brains were extracted and sectioned coronally on a cryostat at 40 um. Immunohistochemistry was used to fluorescently label CC1 and NG2 (which are used to identify oligodendrocytes (OL) and oligodendrocyte precursor cells (OPC), respectively). Unbiased stereological approaches will be used to quantify cumulative labeled axon length as well as total OL and OPC populations in Re. This study will provide us with additional information on how alcohol exposure impacts these executive function-related brain regions, as well as the effectiveness of combined exercise and environmental complexity as a useful intervention for individuals with FASD.