GluN2A Mediated PS-Induced Depressive-Like Behavior Through Ca ²⁺ Overload Inhibited Myelinization

Prenatal stress (PS) could induce depression in offspring, however, the underlying mechanism still need to be illustrated. In this study, we established a prenatal restraint stress rat model and examined depressive-like behavior in offspring rats. Moreover, we examined GluN2A-type NMDA receptor Ca2+ signaling and myelin basic protein (MBP) expression. Our results indicated that glutamate level was significantly increased in offspring rats in PS-S group, GluN2A-type NMDA receptor Ca2+ signaling was disturbance in hippocampus. The optical density of MBP staining, MBP mRNA, MBP protein expression levels were decreased which showed that myelinization in hippocampus was impaired. After treated rats with GluN2A receptor antagonist, NVP-AAM077 elicited remarkable antidepressant-like effects in OFT and FST, as well as a rescue of GluN2A, MBP and p-CaMKII abnormity. These findings suggest that GluN2A could be a promising target for the development of pharmacotherapies for PS induced depression.