Major depressive disorder (MDD) is a prevalent psychiatric condition with a significant global impact, contributing to increasing morbidity and mortality. Inhibition of cannabinoid receptor 1 (CB1R) has been linked to both depression and anxiety, but the underlying mechanisms remain elusive. Recently, we identified Neurensin-2, a novel depression-associated protein expressed in CCK inhibitory interneurons in the hippocampus, which also highly express CB1R. Neurensin-2, a stress-responsive vesicular protein, putatively plays a role in protein trafficking; however, its involvement in regulating depression and anxiety is not well understood. In my unpublished work, we found evidence that Neurensin-2 regulates CB1R. Thus, my PhD research focuses on the role of Neurensin-2 in regulating cannabinoid signaling in vitro and in vivo. We will employ a multidisciplinary approach that integrates bioinformatics, molecular biology, pharmacology, behavioral analysis, as well as physiological and genetic manipulation techniques. We will demonstrate that Neurensin-2 in hippocampal inhibitory interneurons regulates the cannabinoids singling to mediate depression and anxiety-related behaviors. We expect that this project will significantly enhance our current understanding of the pathophysiology of depression and anxiety. These findings will open new avenues for developing improved, cell-type-specific treatments for these disorders.

Supervisor: Gali Umshweif-Nevo