Specifically, the ALKBH5 levels were increased in the blood and PFC of MDD patients as well as in the mouse models of depression; ALKBH5 in astrocytes is more sensitive to stress compared to that in neurons and endothelial cells; selective knockout of ALKBH5 in astrocytes, but not in neurons and endothelial cells, produces antidepressant-like behaviors; and under chronic stress, astrocytic ALKBH5 preserved neuronal morphology, calcium activity and glutamatergic transmission through GLT-1 m6A modifications. Here, ALKBH5 is linked to depressive disorder.