Astrocytic <scp>FABP7</scp> Alleviates Depression‐Like Behaviors of Chronic Unpredictable Mild Stress Mice by Regulating Neuroinflammation and Hippocampal Spinogenesis

Fatty acid binding protein 7 (FABP7) is prominently expressed in astrocytes and is a critical regulator of inflammatory responses. Accumulating evidence suggests that FABP7 is crucial in neuropsychological disease through the modulation of spinogenesis. Nonetheless, the impact of FABP7 on depressive disorders and the underlying mechanisms is not fully understood. Here, we investigated the antidepressant properties of FABP7 using the chronic unpredictable mild stress (CUMS)-induced model of depression and possible mechanisms. Our results revealed that depressive-like behavior induced by CUMS was associated with decreased levels of FABP7 protein in the hippocampus (HP). Furthermore, the overexpression of FABP7 in the HP mitigated the depressive-like behavior and increased the expression of its downstream target caveolin-1 (Cav-1). FABP7 overexpression in the HP specifically regulates the expression of the astrocyte marker protein GFAP, as well as the blood-brain barrier (BBB)-associated proteins AQP4, CLDN-5, occludin, and LRP1. Notably, the CUMS-induced upregulation of the pro-inflammatory factors IL-1β and IL-6 was also significantly reversed by FABP7 overexpression in the HP. This intervention also led to increased levels of postsynaptic proteins, including PSD95 and GluA1, as well as an increase in brain-derived neurotrophic factor (BDNF) and enhanced neuronal dendritic spine density. The findings indicate that FABP7 exerts antidepressant-like properties by inhibiting inflammation, regulating spinogenesis, and modulating BBB-related proteins.