Inhibition of microglial glutaminase alleviates chronic stress-induced neurobehavioral and cognitive deficits.

ABSTRACT: Major depressive disorder (MDD) is a prevalent and debilitating psychiatric condition with significant societal and economic impacts. Many patients are resistant to current antidepressant therapies, underscoring the need for novel treatments targeting underlying mechanisms. We previously discovered that glutaminase (GLS1), an enzyme converting glutamine to glutamate, is upregulated specifically in activated microglia in mice exposed to Chronic Social Defeat Stress (CSDS). Importantly, GLS1 mRNA was also upregulated in microglia within postmortem brain tissue of MDD patients, highlighting a potential role for microglial GLS1 in MDD pathophysiology. However, existing GLS1 inhibitors lack brain penetrance and/or cause gastrointestinal toxicities, limiting their translational potential. To add

SUBMITTER: Huang M 

PROVIDER: S-EPMC12664560 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature