Major depressive disorder (MDD) is a prevalent psychiatric condition with a significant global impact, contributing to increasing morbidity and mortality.
Recently, we identified Neurensin-2, a novel, stress-responsive vesicular protein enriched in hippocampal inhibitory interneurons that highly express cannabinoid receptor 1 (CB1R) and are implicated in mood regulation. Dysregulation of the CB1R has been implicated in both depression and anxiety, yet the molecular mechanisms remain poorly understood. Although Neurensin-2 has been proposed to function in protein trafficking, its role in the modulation of affective disorders is largely unexplored. Preliminary data from my unpublished work suggest that Neurensin-2 regulates CB1R expression and signaling. My PhD research focuses on the role of Neurensin-2 in the regulation of cannabinoid signaling under stress-related conditions, both 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 cannabinoid signaling to mediate depression and anxiety-related behaviors.
This research is expected to advance our understanding of the cellular and molecular basis of mood disorders and will open new avenues for the development of novel, cell-type-specific therapeutic strategies.

Supervisor: Gali Umshweif-Nevo