In this study, we hypothesized that TNF-α activated astrocytes to progress to the A1 type by binding to its pro-inflammatory specific receptor, TNFR1, to induce the development of depression-like behavior in chronic unpredictable mild stress (CUMS) mice, whereas Rho could “block” the process of this pathophysiology, by acting as an antidepressant. The gene discussed is RHO; the disease is major depressive disorder.