Isoflurane produces antidepressant effects inducing BDNF-TrkB signaling in CUMS mice
Abstract
Rationale The volatile anesthetic isoflurane is suggested to produce a rapid and robust antidepressive effect in preliminary clinical trials. Recently, isoflurane was found to activate the tropomyosin receptor kinase B (TrkB) signaling which is the underlying mechanism of the rapid antidepressant ketamine. Objective Our study investigated the effect of isoflurane anesthesia on chronic unpredictable mild stressed (CUMS) model in mice and verified the role of brain-derived neurotrophic factor (BDNF)/TrkB/ the mammalian target of rapamycin (mTOR) signaling in the antidepressant effect of isoflurane. Methods We employed the CUMS model of depression to assess the rapid antidepressant effect of isoflurane by the forced swimming test (FST), the sucrose preference test (SPT), and the novelty suppressed feeding test (NSFT). The protein expression of BDNF and TrkB/protein kinase B (PKB or Akt)/mTOR was determined through Western blot. The dendritic spine density in the hippocampus and medial prefrontal cortex (PFC) was measured by the Golgi staining. Results A brief burst-suppressing isoflurane anesthesia rapidly reversed the behavioral deficits caused by CUMS procedure, normalized the expression of BDNF and further activated the TrkB signaling pathway in CUMS-induced stressed mice in both prefrontal cortex (PFC) and hippocampus (HC). All of those behavioral and proteomic effects were blocked by K252a, a selective receptor inhibitor of TrkB. Isoflurane significantly promoted the formation of dendritic spines in both medial prefrontal cortex (mPFC), CA1, CA3, and DG of the hippocampus. Conclusion Our study indicates that isoflurane exerts a rapid antidepressant-like effect in CUMS depression animal model, and the activation of BDNF/TrkB signaling pathway plays an indispensable role in the biological and behavioral antidepressant effects of isoflurane. A single exposure to isoflurane could repair synaptic damage caused by chronic stimulation.
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Several volatile anesthetics, such as isoflurane, nitrous oxide, propofol, and xenon, may produce rapid antidepressant effects.
“Several volatile anesthetics, such as isoflurane, nitrous oxide, propofol, and xenon, may produce rapid antidepressant effects (157–165).”
From Psychedelics and Other Psychoplastogens for Treating Mental Illness. (2021) · cites this paper as [165]
Isoflurane's antidepressant effects appear to be mediated via TrkB signaling and subsequent increases in dendritic spine density in the PFC and hippocampus.
“these effects appear to be mediated via TrkB signaling and subsequent increases in dendritic spine density in the PFC and hippocampus (164, 165)”
From Psychedelics and Other Psychoplastogens for Treating Mental Illness. (2021) · cites this paper as [165]
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Psychedelics and Other Psychoplastogens for Treating Mental Illness.
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- Authors
- Zhang, S.-S., Tian, Y.-H., Jin, S.-J., Wang, W.-C., Zhao, J.-X., Si, X.-M., Zhang, L., Xu, H., & Jin, J.-Y.
- Affiliations
- Chinese Academy of Sciences (CN)
- Qingdao University (CN)
- Corresponding author
- Jin, Jing-Yu
- ORCID
- Venue
- Psychopharmacology
- Published
- 2019-06-13
- Volume
- 236
- Issue
- 11
- Pages
- 3301-3315
- ISSN
- 0033-3158 (ISSN-L)
- 1432-2072
- OpenAlex
- W2949340001
- Cited by
- 49
- References
- 11
- Citations by year
- 2026: 6 · 2025: 4 · 2024: 8 · 2023: 7 · 2022: 5 · 2021: 11 · 2020: 5 · 2019: 2 · 2018: 1
- FWCI
- 3.58
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Psychopharmacology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Natural Science Foundation of China (No. 31272397)
- Natural Science Foundation of Shandong Province (No. ZR2011CM041)
- Qingdao Postdoctoral Application Research Project
- Topics
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Life Sciences › Neuroscience › Developmental Neuroscience › Anesthesia and Neurotoxicity Research
- Health Sciences › Medicine › Psychiatry and Mental health › Electroconvulsive Therapy Studies
- Keywords
- isoflurane, antidepressant effects, BDNF/TrkB signaling, chronic unpredictable mild stress, depression, mTOR signaling, dendritic spines, hippocampus, medial prefrontal cortex, volatile anesthetics, synaptic damage, K252a
- MeSH terms
- Animals, Antidepressive Agents, Depression, Dose-Response Relationship, Drug, Isoflurane, Male, Membrane Glycoproteins, Mice, Inbred C57BL, Protein-Tyrosine Kinases, Random Allocation, Stress, Psychological, Signal Transduction, Anesthetics, Inhalation, Brain-Derived Neurotrophic Factor, Receptor, trkB, Mice
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