JHU-083 selectively blocks glutaminase activity in brain CD11b⁺ cells and prevents depression-associated behaviors induced by chronic social defeat stress.

ABSTRACT: There are a number of clinically effective treatments for stress-associated psychiatric diseases, including major depressive disorder (MDD). Nonetheless, many patients exhibit resistance to first-line interventions calling for novel interventions based on pathological mechanisms. Accumulating evidence implicates altered glutamate signaling in MDD pathophysiology, suggesting that modulation of glutamate signaling cascades may offer novel therapeutic potential. Here we report that JHU-083, our recently developed prodrug of the glutaminase inhibitor 6-diazo-5-oxo-L-norleucine (DON) ameliorates social avoidance and anhedonia-like behaviors in mice subjected to chronic social defeat stress (CSDS). JHU-083 normalized CSDS-induced increases in glutaminase activity specifically in microglia-enrich

SUBMITTER: Zhu X 

PROVIDER: S-EPMC6372721 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature