ArticleScientific reports2023
Exploring the role of esketamine in alleviating depressive symptoms in mice via the PGC-1α/irisin/ERK1/2 signaling pathway.
Article in Scientific reports, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.
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Who cites it
3 citing papers in PubMed, 9 citations in OpenAlex.
- CircKat6b Mediates the Antidepressant Effect of Esketamine by Regulating Astrocyte Function.Molecular neurobiology · 2025Article
- The Impact of Esketamine on Depression: Targeting Oxidative Stress and Neuronal Apoptosis Through BDNF/TrkB/PI3K/AKT Pathway Activation.Neuropsychiatric disease and treatment · 2025Article
- Mitochondria in depression: The dysfunction of mitochondrial energy metabolism and quality control systems.CNS neuroscience & therapeutics · 2024Review
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Esketamine provides an immediate and noticeable antidepressant effect, although the underlying molecular processes are yet unclear. Irisin induced by aerobic exercise has been implicated in the alleviation of depressive symptoms, whether irisin expression responds to the administration of esketamine remains unknown. In this study, we found that irisin was reduced in the hippocampus and peripheral blood of chronic unpredictable mild stress (CUMS) mice, whereas the irisin level was rescued by esketamine treatment. The reduction of PGC-1α expression (transcriptional regulator of irisin gene expression) in the CUMS mice was rescued by esketamine treatment, PGC-1α knockdown significantly reduced the irisin level induced by esketamine. Additionally, FNDC5/irisin-knockout mice developed more severe depressant-like behaviors than wild-type mice under CUMS stimulation, with an attenuated the antidepressant effect of esketamine. Further research indicated that irisin-mediated modulation of esketamine on depressive-like behaviors in CUMS mice involved the ERK1/2 pathway. Overall, the PGC-1α/irisin/ERK1/2 signaling activation may be a new mechanism underlying the antidepressant activity of esketamine, denoting that irisin may be a promising therapeutic target for the treatment of depression.
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