Pinna Antonello, Kistowska Julia, Pałasz Artur
Department of Histology, Faculty of Medical Sciences in Katowice, Medical University of Silesia, ul. Medyków 18, 40-752, Katowice, Poland.
Neuromolecular Med. 2025 Aug 8;27(1):58. doi: 10.1007/s12017-025-08880-y.
Depression is a leading global cause of disability. Emerging evidence highlights glutamatergic dysfunction, particularly impaired NMDA receptor signaling, as a key contributor to its neurobiology. Hydrogen sulfide (H₂S), once regarded solely as toxic, is now recognized for its role in regulating synaptic plasticity, inflammation, and neuronal survival. This review synthesizes recent findings on the antidepressant effects of H₂S. In animal models, H₂S administration improves depression-like behaviors while modulating key pathways such as PI3K/AKT/mTOR, Sirt1, and the cGAS-STING pathway. These benefits extend across models of stress, neuropathic pain, diabetes, and sleep deprivation. Among H₂S donors, sodium hydrosulfide (NaHS) demonstrated the most consistent antidepressant effects in preclinical studies. Clinical studies further show that individuals with major depression exhibit lower plasma H₂S levels, with symptom severity inversely correlated to H₂S concentration. Together, these findings support a multifaceted role for H₂S in mood regulation and highlight its promise as both a therapeutic candidate and a potential biomarker in depressive disorders, though translational studies remain needed.
抑郁症是导致全球残疾的主要原因。新出现的证据表明，谷氨酸能功能障碍，尤其是N-甲基-D-天冬氨酸（NMDA）受体信号受损，是其神经生物学的关键因素。硫化氢（H₂S）曾被认为是有毒物质，现在人们认识到它在调节突触可塑性、炎症和神经元存活方面的作用。这篇综述总结了关于H₂S抗抑郁作用的最新研究结果。在动物模型中，给予H₂S可改善抑郁样行为，同时调节关键信号通路，如PI3K/AKT/mTOR、Sirt1和cGAS-STING信号通路。这些益处适用于应激、神经性疼痛、糖尿病和睡眠剥夺等多种模型。在H₂S供体中，硫氢化钠（NaHS）在临床前研究中显示出最一致的抗抑郁作用。临床研究进一步表明，重度抑郁症患者的血浆H₂S水平较低，症状严重程度与H₂S浓度呈负相关。这些研究结果共同支持了H₂S在情绪调节中的多方面作用，并突出了其作为抑郁症治疗候选药物和潜在生物标志物的前景，不过仍需要进行转化研究。
