Mental illness stems from intricate interactions between genes and the environment. Prenatal alcohol exposure is most common environmental input that leads to disorders of the brain and behavior. Fetal Alcohol Spectrum Disorder (FASD) collectively describes all the defects caused by prenatal alcohol exposure. In the United States it is estimated that 1 in 100 children have FASD. Impaired social behavior is a frequent and debilitating symptom of FASD. The risk of FASD is modified by an individual's genetics, with some deficits being linked to impairments of neurotransmitter systems such as dopamine. However, the exact mechanisms for FASD social deficits are unknown. My host lab has shown that elevating mTORC1 signaling rescues ethanol-induced facial defects in zebrafish. Using zebrafish, I have shown that a two-hour developmental exposure to 1% ethanol (resulting in tissue levels of approximately 27 mM ethanol), which is comparable to established rodent FASD exposure leads to permanent social deficits and disrupted dopamine functioning. Thus, I joined my host lab to characterize the genetic predisposition to ethanol-induced social behavior deficits. I will test the hypothesis that ethanol attenuates the overall level of mechanistic target-of-rapamycin (mTOR) pathway signaling which regulates development of the dopaminergic system and, subsequently social behavior. Collectively my results will provide mechanistic insight into one of the most devastating human disorders which, has a life-long impact on the brain and behavior.
The purpose of this proposal is to elucidate the genetics and mechanisms underlying the social defects found in patients with Fetal Alcohol Spectrum Disorders (FASD). Results obtained from this proposal will greatly increase our understanding of gene-ethanol interactions and the etiology of FASD social defects.
