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

Han Qin, Miao Yu, Nianjiao Han, Meilin Zhu, Xia Li, Jing Zhou

Progress in neuro-psychopharmacology & biological psychiatry June 8, 2024 DOI: 10.1016/j.pnpbp.2024.110992 (opens in new tab)

Study at a glance

AI-extracted from the abstract
Characteristics Animal study Peer reviewed
Population Mice with postpartum depression and their offspring
Intervention Esketamine
Topics Esketamine Depression
Keywords Bdnf/akt/mtor Postpartum depression ppd Postnatal depression Esketamine spravato Ketamine derivative Neuroscience brain chemistry Neural pathways
Citations 27
Key points Esketamine ameliorated anxiety- and depression-like behaviors and restored impaired BDNF/AKT/mTOR signaling in the frontal and hippocampal regions of mice with PPD and their offspring.

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.

Comparable studies

Other preclinical and animal studies on esketamine for depression, most cited first.

Study Year Design Participants
Low-dose S-ketamine exerts antidepressant-like effects via enhanced hippocampal synaptic plasticity in postpartum depression rats. Rat model of postpartum depression induced by reproductive hormone withdrawal 2022 Animal study
Electroconvulsive therapy combined with esketamine improved depression through PI3K/AKT/GLT-1 pathway. Human patients with severe depression and a rat model of depression 2025 Randomized controlled trial and animal study n = 12
S-ketamine Alleviates Neuroinflammation and Attenuates Lipopolysaccharide-Induced Depression Via Targeting SIRT2. Lipopolysaccharide (LPS)-induced mouse model 2025 Animal study with in vitro and in vivo experiments
Esketamine alleviates LPS-induced depression-like behavior by activating Nrf2-mediated anti-inflammatory response in adolescent mice. Adolescent male C57BL/6J mice 2025 Preclinical experimental study
S-ketamine alleviates depression-like behavior and hippocampal neuroplasticity in the offspring of mice that experience prenatal stress. Male offspring of pregnant rats subjected to chronic unpredictable mild stress 2024 Animal study

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