IL-10 rescues early-life stress-driven depression-like behavior via restoring lateral habenula GABAA receptor function

Ruxuan Ding

Department of Anatomy, School of Medicine, Sun Yat-sen University, Shenzhen, Guangdong, China 

To investigate how maternal separation (MS) changes anti-inflammatory IL-¹⁰ levels and evaluate its role in regulating lateral habenula (LHb) neuronal activity and depressive-like behaviors. Chemogentic and viral vector tools, targeting IL-¹⁰/IL-¹⁰R cascade manipulation, were conducted on Fos-trap mice, to assess the effect of LHb IL-¹⁰ on depression-like behavior. The results showed that MS dampened the LHb IL-¹⁰ level, consequently reducing GABAAR β² at the S⁴¹⁰ site phosphorylation level via IL-¹⁰R/PI³K/AKT/pathway, enhancing Fos expression and vulnerability to depression-like behavior in mice.