An Enigma of Brain Gasotransmitters: Hydrogen Sulfide and Depression

Al-Owais, M. M., Hettiarachchi, N. T., Dallas, M. L., Scragg, J. L., Lippiat, J. D., Holden, A. V., Steele, D. S., & Peers, C. (2023). Inhibition of the voltage-gated potassium channel Kv1.5 by hydrogen sulfide attenuates remodeling through S-nitrosylation-mediated signaling. Communications Biology, 6(1), 651. https://doi.org/10.1038/s42003-023-05016-5

Article  CAS  PubMed  PubMed Central  Google Scholar 

Amidfar, M., Woelfer, M., Réus, G. Z., Quevedo, J., Walter, M., & Kim, Y. K. (2019). The role of NMDA receptor in neurobiology and treatment of major depressive disorder: Evidence from translational research. Progress in Neuro-Psychopharmacology and Biological Psychiatry, 94, 109668. https://doi.org/10.1016/j.pnpbp.2019.109668

Article  CAS  PubMed  Google Scholar 

Azzam, M. A., ElMonier, A. A., Gad, E. S., & Abd-Elmawla, M. A. (2025). Interplay of endoplasmic reticulum stress, inflammation, apoptosis, and oxidative stress in corticosteroid-induced anxiety and depression: Exploring therapeutic potential of hydrogen sulfide and sertraline. ACS Chemical Neuroscience, 16(7), 1361–1376. https://doi.org/10.1021/acschemneuro.5c00057

Article  CAS  PubMed  Google Scholar 

Bai, X., Batallé, G., & Pol, O. (2021). The anxiolytic and antidepressant effects of Diallyl Disulfide and GYY4137 in animals with chronic neuropathic pain. Antioxidants (Basel, Switzerland), 10(7), 1074. https://doi.org/10.3390/antiox10071074

Article  CAS  PubMed  Google Scholar 

Bai, X., Batallé, G., Martínez-Martel, I., & Pol, O. (2023). Hydrogen sulfide interacting with cannabinoid 2 receptors during sciatic nerve injury-induced neuropathic pain. Antioxidants, 12(6), 1179. https://doi.org/10.3390/antiox12061179

Article  CAS  PubMed  PubMed Central  Google Scholar 

Bao, P., Gong, Y., Wang, Y., Xu, M., Qian, Z., Ni, X., & Lu, J. (2023). Hydrogen sulfide prevents LPS-Induced depression-like behavior through the suppression of NLRP3 inflammasome and pyroptosis and the improvement of mitochondrial function in the hippocampus of mice. Biology, 12(8), 1092. https://doi.org/10.3390/biology12081092

Article  CAS  PubMed  PubMed Central  Google Scholar 

Baskin, V., Eroglu, E., Harmanci, N., & Erol, K. (2022). Antinociceptive, anxiolytic, and depression-like effects of hydrogen sulfide, nitric oxide, and carbon monoxide in rats and the role of opioidergic and serotonergic systems in antinociceptive activity. Fundamental and Clinical Pharmacology, 36(4), 674–686. https://doi.org/10.1111/fcp.12763

Article  CAS  PubMed  Google Scholar 

Batallé, G., Bai, X., Pouso-Vázquez, E., Roch, G., Rodríguez, L., & Pol, O. (2021). The recovery of cognitive and affective deficiencies linked with chronic osteoarthritis pain and implicated pathways by slow-releasing hydrogen sulfide treatment. Antioxidants (Basel, Switzerland), 10(10), 1632. https://doi.org/10.3390/antiox10101632

Article  CAS  PubMed  Google Scholar 

Caliendo, G., Cirino, G., Santagada, V., & Wallace, J. L. (2010). Synthesis and biological effects of hydrogen sulfide (H2S): Development of H2S-releasing drugs as pharmaceuticals. Journal of Medicinal Chemistry, 53(17), 6275–6286. https://doi.org/10.1021/jm901638j

Article  CAS  PubMed  Google Scholar 

Chan, N., Willis, A., Kornhauser, N., Ward, M. M., Lee, S. B., Nackos, E., Seo, B. R., Chuang, E., Cigler, T., Moore, A., Donovan, D., Vallee Cobham, M., Fitzpatrick, V., Schneider, S., Wiener, A., Guillaume-Abraham, J., Aljom, E., Zelkowitz, R., Warren, J. D., … Vahdat, L. (2017). Influencing the tumor microenvironment: A phase II study of copper depletion using Tetrathiomolybdate in patients with breast cancer at high risk for recurrence and in preclinical models of lung metastases. Clinical Cancer Research: an Official Journal of the American Association for Cancer Research, 23(3), 666–676. https://doi.org/10.1158/1078-0432.CCR-16-1326

Article  CAS  PubMed  Google Scholar 

Chen, X., Jhee, K. H., & Kruger, W. D. (2004). Production of the neuromodulator H2S by cystathionine beta-synthase via the condensation of cysteine and homocysteine. The Journal of Biological Chemistry, 279(50), 52082–52086. https://doi.org/10.1074/jbc.C400481200

Article  CAS  PubMed  Google Scholar 

Du, L., Chen, L., Luo, B., Chen, Y. J., Zhang, P., Tang, Y. Y., Jiang, J. M., & Zou, W. (2023). Silent information regulator 1 mediates H2S-inhibited chronic restraint stress-induced depressive-like behaviors by regulating hippocampal autophagy. NeuroReport, 34(3), 128–136. https://doi.org/10.1097/WNR.0000000000001870

Article  CAS  PubMed  Google Scholar 

Dutta, S. S., Dasgupta, S., Banerjee, A. K., Nath, I., Biswas, U., Bera, N., & Ruram, A. (2024). Exploring the role of serum hydrogen sulphide (H2S) levels in manic depressive psychosis in terms of its association, diagnostic ability, and severity prediction: findings from a tertiary care center in North Bengal. Cureus, 16(3), e56857. https://doi.org/10.7759/cureus.56857

Article  PubMed  PubMed Central  Google Scholar 

Gu, B., Li, T., Zhao, H., Yue, R., Luo, Q., Yu, S., Li, T., Zhao, Y., Liu, D., Wang, Z., & Ho, C. S. H. (2025). Age-dependent effects of H2S on post-traumatic stress disorder in adolescent and adult mice. Frontiers in Psychiatry, 16, 1546737. https://doi.org/10.3389/fpsyt.2025.1546737

Article  PubMed  PubMed Central  Google Scholar 

Hashimoto, K. (2011). The role of glutamate on the action of antidepressants. Progress in Neuro-Psychopharmacology and Biological Psychiatry, 35(7), 1558–1568. https://doi.org/10.1016/j.pnpbp.2010.06.013

Article  CAS  PubMed  Google Scholar 

He, J., Guo, R., Qiu, P., Su, X., Yan, G., & Feng, J. (2017). Exogenous hydrogen sulfide eliminates spatial memory retrieval impairment and hippocampal CA1 LTD enhancement caused by acute stress via promoting glutamate uptake. Neuroscience, 350, 110–123. https://doi.org/10.1016/j.neuroscience.2017.03.018

Article  CAS  PubMed  Google Scholar 

Jain, S. K., Margret, J. J., Parsanathan, R., & Velusamy, T. (2024). Efficacy of l-cysteine in increasing circulatory hydrogen sulfide, nitrite, and 25-hydroxyvitamin D levels in Zucker diabetic fatty rats and in vitro treatment of hydrogen sulfide and nitrite in upregulating vitamin D hydroxylase genes in monocytes. Journal of Dairy Science, 107(12), 10221–10230. https://doi.org/10.3168/jds.2024-25169

Article  CAS  PubMed  Google Scholar 

Jiang, W., Tang, Y. Y., Zhu, W. W., Li, C., Zhang, P., Li, R. Q., Chen, Y. J., Zou, W., & Tang, X. Q. (2021). PI3K/AKT pathway mediates the antidepressant- and anxiolytic-like roles of hydrogen sulfide in streptozotocin-induced diabetic rats via promoting hippocampal neurogenesis. Neurotoxicology, 85, 201–208. https://doi.org/10.1016/j.neuro.2021.05.016

Article  CAS  PubMed  Google Scholar 

Kang, X., Jiang, L., Lan, F., Tang, Y. Y., Zhang, P., Zou, W., Chen, Y. J., & Tang, X. Q. (2021). Hydrogen sulfide antagonizes sleep deprivation-induced depression- and anxiety-like behaviors by inhibiting neuroinflammation in a hippocampal Sirt1-dependent manner. Brain Research Bulletin, 177, 194–202. https://doi.org/10.1016/j.brainresbull.2021.10.002

Article  CAS  PubMed  Google Scholar 

Kimura, H. (2020). Hydrogen sulfide signalling in the CNS - Comparison with NO. British Journal of Pharmacology, 177(22), 5031–5045. https://doi.org/10.1111/bph.15246

Article  CAS  PubMed  PubMed Central  Google Scholar 

Kimura, H. (2021). Hydrogen sulfide (H2S) and polysulfide (H2Sn) signaling: The first 25 years. Biomolecules, 11(6), 896. https://doi.org/10.3390/biom11060896

Article  CAS  PubMed  PubMed Central  Google Scholar 

Kolluru, G. K., Shen, X., Bir, S. C., & Kevil, C. G. (2013). Hydrogen sulfide chemical biology: Pathophysiological roles and detection. Nitric Oxide, 35, 5–20. https://doi.org/10.1016/j.niox.2013.07.002

Article  CAS  PubMed  PubMed Central  Google Scholar 

Ling, Z., Kong, Q., He, Z., Hao, X., Liu, R., Liu, J., Wang, Y., Liu, J., Du, W., & Liu, Y. (2025). Hydrogen sulfide improves depression-like behaviors in CUMS-induced mice by regulating autophagy. Psychoneuroendocrinology, 175, 107418. https://doi.org/10.1016/j.psyneuen.2025.107418

Article  CAS  PubMed  Google Scholar 

Liu, F., Tian, Q., Tang, H. L., Cheng, X., Zou, W., & Zhang, P. (2024). Hydrogen sulfide attenuates depression-like behaviours in Parkinson’s disease model rats by improving synaptic plasticity in a hippocampal Warburg effect-dependent manner. Pharmacology, Biochemistry, and Behavior, 234, 173677. https://doi.org/10.1016/j.pbb.2023.173677

Article  CAS  PubMed  Google Scholar 

Luo, B., Xie, Y., Kuang, W., Wang, Y., Chen, G., Zhang, Y., & Yuan, M. (2025). Hydrogen sulfide improves poststroke depression-induced inflammation in microglial cells by enhancing endoplasmic reticulum autophagy and inhibiting the cGAS-STING pathway. NeuroReport, 36(6), 314–326. https://doi.org/10.1097/WNR.0000000000002152

Article  CAS 

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