This project will use state-of-the-art neuroimaging tools combined with a computational model to examine the underlying mechanisms associated with cognitive and behavioral effects of prenatal alcohol exposure gaining insight from the other center projects. The long-term goal is to understand the neurophysiological underpinnings of cognitive deficits to guide treatment development for individuals affected by prenatal alcohol exposure.
The proposed studies will contribute to public health by identifying functional, structural, and molecular targets for treating cognitive deficits associated with fetal alcohol spectrum disorders (FASD). These studies will determine the consequences of prenatal alcohol exposure on a key brain circuit that regulates working memory and decision-making, and will provide new avenues for treating individuals with FASD.
Emerging evidence from both preclinical and clinical studies supports that the biological vulnerability to chronic central nervous system (CNS) dysfunction in FASD populations is driven by aberrant CNS-immune interactions, rendering them particularly susceptible to developing cognitive disabilities during the period of adolescence, often manifesting after secondary challenges such as stress or immune challenges. While the underlying mechanism of adolescent cognitive deficits from prenatal alcohol exposure (PAE) is unknown, the proposed research will identify whether non-coding circular RNAs underlie sensitized CNS-inflammatory immune signaling pathways, potentially inclusive of TLR4-associated factors from PAE that lead to cognitive deficits. Exploring these novel molecular targets in preclinical models, along with leveraging clinical data from adolescent children with FASD, will provide a foundation to develop future therapeutic targets to treat adolescent cognitive deficits as well as identify biomarkers of adolescent cognitive dysfunction for early intervention to mitigate the impact PAE exerts on cognitive function.
Prenatal alcohol exposure (PAE) is the most common environmental cause of neurodevelopmental brain injury, resulting in the development of fetal alcohol spectrum disorders (FASDs). Children with FASD exhibit persistent learning and behavioral disabilities, which may be due to white matter injury in the brain. The goal of our study is to investigate how alcohol impacts the gene expression and function of oligodendrocytes, the major glial cell type that is responsible for myelinating white matter tracts in a mouse model of FASD.
New Mexico Alcohol Research Center