A model of Akt-mTOR signaling pathways in developing PPD potentiated by prepregnancy stress.
Chronic mild stress results in up-regulation of NMDA receptor subunit NR1, which suppresses the activation of Akt, in turn down-regulates mTOR signaling in the hippocampus. This abnormal signaling underscores the depressive-like behavior, although the deficit can be gradually restored, responsible for behavioral recovery. With the occurrence of parturition, the chronic stress, however, facilitates a prolonged NR1/Akt/mTOR signaling deficiency and neurogenesis postpartum, subsequently induces a long-term postpartum depression. The defect Akt-mTOR signaling can be corrected by a single dose of ketamine and thus a quick and enduring antidepressant effect is achieved.