Antidepressant effects of esketamine via the BDNF/AKT/mTOR pathway in mice with postpartum depression and their offspring.

Esketamine, a drug approved for treatment-resistant depression, may also treat postpartum depression (PPD) and reduce depression risk in offspring. In a mouse model of chronic unpredictable mild stress during pregnancy, both mothers with PPD and their adult offspring showed anxiety- and depression-like behaviors. Injecting esketamine into postpartum mice improved these behaviors: it enhanced exploration in unfamiliar environments, increased preference for sucrose, and restored impaired BDNF/AKT/mTOR signaling in the frontal lobe and hippocampus. The findings suggest esketamine has potential for treating PPD and lowering the incidence of depression in the next generation.

Study at a glance

Abstract

Postpartum depression (PPD) is a serious mental health problem that can negatively affect future generations. BDNF/AKT/mTOR signaling in the frontal lobe and hippocampus in mice is associated with depression, but its role in mice with PPD and their offspring is unknown. This study was aimed at investigating the effects of esketamine (ESK), a drug approved for treatment of refractory depression, on the BDNF/AKT/mTOR pathway in mice with PPD and their offspring. A model of chronic unpredictable mild stress with pregnancy was used. ESK was injected into postpartum mice, and behavioral tests were conducted to predict the severity of symptoms at the end of lactation and in the offspring after adulthood. Both mice with PPD and their offspring showed significant anxiety- and depression-like behaviors that were ameliorated with the ESK intervention. ESK enhanced exploratory behavior in unfamiliar environments, increased the preference for sucrose, and ameliorated the impaired BDNF/AKT/mTOR signaling in the frontal and hippocampal regions in mice. Thus, ESK may have great potential in treating PPD and decreasing the incidence of depression in offspring.