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Exploring Esketamine's Therapeutic Role for Perinatal Depression via TASK-1 Tandem Pore Potassium Channels.

Lin Zhu, Ji Chen, Yuan Liu, Wen Chen, Xinxin Liu, Fengrui Yang

ACS Chemical Neuroscience July 29, 2025 DOI: 10.1021/acschemneuro.5c00535 (opens in new tab)

Study at a glance

AI-extracted from the abstract
Characteristics Integrates clinical and preclinical approaches Peer reviewed
Sample size 298
Population Full-term pregnant women with perinatal depression
Intervention Esketamine
Topics Esketamine Neuroplasticity Depression
Keywords Neuroinflammation New approach Lowers depression scores New mothers Combats perinatal depression Improved mental well-being Therapeutic avenue Esketamine mechanism esketamine How esketamine works Targeting Mediated by
Citations 1
Key points Esketamine lowers depression scores in perinatal depression through modulation of TASK-1 potassium channels, reducing neuroinflammation and altering synaptic plasticity.

Abstract

This research focuses on the promising use of esketamine in perinatal depression, a widespread disorder impacting postpartum women's mental health. Despite esketamine's known rapid antidepressant effects, its precise mechanisms are not fully understood. This study integrates clinical and preclinical approaches to explore esketamine's efficacy in treating perinatal depression and its actions associated with TASK-1 potassium channels. A total of298 full-term pregnant women participated in a clinical trial, revealing that esketamine significantly lowers depression scores compared to controls. Alongside, mouse models were used to assess behavioral changes post-treatment, with findings highlighting reduced neuroinflammation and depressive-like symptoms, attributable to modulation via TASK-1 channels. Advanced gene expression analyses and cultured neuronal cell studies corroborated these findings, particularly through the modulation of synaptic plasticity proteins. Thus, esketamine offers a compelling therapeutic avenue for perinatal depression, with its effectiveness linked to specific neural pathways, encouraging further research and potential therapeutic developments.

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
Antidepressant effects of esketamine via the BDNF/AKT/mTOR pathway in mice with postpartum depression and their offspring. Mice with postpartum depression and their offspring 2024 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

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