In conclusion, our study showed that ADAM10 is also expressed in OPCs, and conditional knockout of ADAM10 in OPCs suppresses proliferation and promotes premature OPCs and premyelination through inactivation of the Notch-1 signaling pathway, inducing the inability of myelination maintenance and leading to “anxiety and depression-like” performance in mice. Here, NOTCH1 is linked to major depressive disorder.