The June 2020 highlighted “VTPP Science in Action” article (link included above and below) comes from the laboratory of Dr. Jayanth Ramadoss. The manuscript outlines a series of elegant experiments designed to investigate the role of mTOR signaling and downstream pathways in the fetal hippocampus following gestational alcohol exposure. Indeed, detailed analysis revealed thatalcohol exposure resulted in dysregulation of mTORC1 signaling specifically in the fetal hippocampus. Figure 5 (below) schematically presents the current understanding of mTOR signaling in the context of gestational alcohol exposure as presented in the Ramadoss paper.
Chronic binge alcohol exposure during pregnancy alters mTOR system in rat fetal hippocampus. The phosphorylation level of mTOR (P-mTOR) in the fetal hippocampus is decreased in the alcohol treated group compared with pair-fed (PF) controls. Alcohol exposure resulted in the altered regulation of fetal hippocampal mTORC1 signaling, demonstrated by an increase in total 4E-BP1 expression. The phosphorylation of second messengers 4E-BP1 and p70 S6K were also increased following gestational alcohol exposure. DEPTOR (an endogenous inhibitor of mTOR) expression levels in the fetal hippocampus were increased; however, RAPTOR was not altered by chronic binge alcohol exposure. The exciting findings presented in this manuscript implicate hippocampal mTOR signaling in fetal hippocampal neurodevelopment which is disrupted in the context of FASD. The discoveries may provide novel insight into the development of targeted pharmacological therapeutic strategies for FASD. Congratulations again to all the members of the Ramadoss laboratory on highly impactful work. https://onlinelibrary.wiley.com/doi/pdf/10.1111/acer.14348