Neuroimmune Interactions in Fetal Alcohol Spectrum Disorders: Potential Therapeutic Targets and Intervention Strategies.

Abstract

Fetal alcohol spectrum disorders (FASD) are a set of abnormalities caused by prenatal exposure to ethanol and are characterized by developmental defects in the brain that lead to various overt and non-overt physiological abnormalities. Growing evidence suggests that in utero alcohol exposure induces functional and structural abnormalities in gliogenesis and neuron-glia interactions, suggesting a possible role of glial cell pathologies in the development of FASD. However, the molecular mechanisms of neuron-glia interactions that lead to the development of FASD are not clearly understood. In this review, we discuss glial cell pathologies with a particular emphasis on microglia, primary resident immune cells in the brain. Additionally, we examine the involvement of several neuroimmune molecules released by glial cells, their signaling pathways, and epigenetic mechanisms responsible for FASD-related alteration in brain functions. Growing evidence suggests that extracellular vesicles (EVs) play a crucial role in the communication between cells via transporting bioactive cargo from one cell to the other. This review emphasizes the role of EVs in the context of neuron-glia interactions during prenatal alcohol exposure. Finally, some potential applications involving nutritional, pharmacological, cell-based, and exosome-based therapies in the treatment of FASD are discussed.