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

Progress in neuro-psychopharmacology & biological psychiatry  – June 08, 2024

Source: PubMed

Summary

Esketamine shows promise in treating postpartum depression, not just for mothers but potentially protecting their children from future mental health issues. The drug works by activating important brain signaling pathways, particularly BDNF/AKT/mTOR, which regulate mood and behavior. Tests in mice revealed that esketamine treatment improved both mothers' depression symptoms and their offspring's emotional well-being into adulthood.

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.

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