Axon Growth in Fetal Alcohol Spectrum Disorder

While any amount of prenatal alcohol exposure (PAE) negatively affects fetal functioning and development, pregnant individuals continue to consume alcohol. PAE often leads to Fetal Alcohol Spectrum Disorder (FASD), a range of effects from severe physiological abnormalities to mild cognitive functioning difficulties. While the outward manifestations of FASD are clear, it is less understood what happens on the molecular and cellular level. Here, we investigate the growth and guidance of two axon populations in a mouse model: thalamocortical axons (TCAs) crossing the pallium-subpallium boundary (PSPB) and dopamine axons entering the subpallium. We hypothesized that both TCAs and dopamine axons would be affected by prenatal ethanol, with TCAs showing abnormal crossing at the PSPB, and fewer dopamine axons entering the subpallium. L1, which stains three axon tracts – thalamocortical, corticothalamic and corticospinal – showed a significant effect of alcohol on axon crossing with opposite effects in males and females. Ethanol-exposed males had a stronger staining intensity than controls while ethanol-exposed females had a weaker staining intensity. Stronger intensity likely corresponds to more crossing, as the stronger intensity is picking up more concentrated axons present at the boundary. Netrin-G1, a TCA-specific stain, provided no significant results. Therefore, we presume that the alcohol effects seen in L1 can be explained by one of the other two axon tracts, corticothalamic or corticospinal. Tyrosine hydroxylase (TH) stains dopaminergic axons and cell bodies, allowing us to trace axons from the midbrain to the subpallium to determine whether they are developing properly. We are in the process of measuring TH-stained axons. Investigating these axon populations can help us to better understand the cellular basis for the behavioral and cognitive deficits present in FASD