Göntér Kitti, Kormos Viktória, Pintér Erika, Pozsgai Gábor
Department of Pharmacology and Pharmacotherapy, Medical School, University of Pécs, H-7624 Pécs, Hungary.
Department of Pharmacology, Faculty of Pharmacy, University of Pécs, H-7624 Pécs, Hungary.
Pharmaceutics. 2025 Jun 14;17(6):781. doi: 10.3390/pharmaceutics17060781.
: Dimethyl trisulfide (DMTS) is a naturally occurring polysulfide with known antioxidant and neuroprotective properties. DMTS is a lipophilic transient receptor potential ankyrin 1 (TRPA1) ligand that reaches the central nervous system (CNS). Its role in the CNS, particularly regarding depression-like behaviour, has yet to be explored. This study investigates the influence of DMTS on stress responses and whether this effect is mediated through the TRPA1 ion channel, known for its role in stress adaptation. Using a mouse model involving three-week exposure, we examined the impact of DMTS on depression-like behaviour and anxiety and identified the involved brain regions. : Our methods involved testing both -wild-type and gene-knockout mice under CUMS conditions and DMTS treatment. DMTS was administered intraperitoneally at a dose of 30 mg/kg on days 16 and 20 of the 21-day CUMS protocol-in hourly injections seven times to ensure sustained exposure. Various behavioural assessments-including the open field, marble burying, tail suspension, forced swim, and sucrose preference tests-were performed to evaluate anxiety and depression-like behaviour. Additionally, we measured body weight changes and the relative weights of the thymus and adrenal glands, while serum levels of corticosterone and adrenocorticotropic hormone were quantified via ELISA. FOSB (FBJ murine osteosarcoma viral oncogene homolog B) immunohistochemistry was utilised to assess chronic neuronal activation in stress-relevant brain areas. : Results showed that CUMS induces depression-like behaviour, with the response being modulated by the TRPA1 status and that DMTS treatment significantly reduced these effects when TRPA1 channels were functional. DMTS also mitigated thymus involution due to hypothalamic-pituitary-adrenal (HPA) axis dysregulation. : Overall, DMTS appears to relieve depressive and anxiety symptoms through TRPA1-mediated pathways, suggesting its potential as a dietary supplement or adjunct therapy for depression and anxiety.
二甲基三硫醚（DMTS）是一种天然存在的多硫化物，具有已知的抗氧化和神经保护特性。DMTS是一种亲脂性的瞬时受体电位锚蛋白1（TRPA1）配体，可进入中枢神经系统（CNS）。其在中枢神经系统中的作用，特别是与抑郁样行为相关的作用，尚未得到探索。本研究调查了DMTS对应激反应的影响，以及这种作用是否通过TRPA1离子通道介导，TRPA1离子通道在应激适应中发挥作用。使用一个涉及三周暴露的小鼠模型，我们研究了DMTS对抑郁样行为和焦虑的影响，并确定了相关的脑区。
我们的方法包括在慢性不可预测温和应激（CUMS）条件和DMTS处理下对野生型和基因敲除小鼠进行测试。在21天的CUMS实验方案的第16天和第20天，以30mg/kg的剂量腹腔注射DMTS，每小时注射一次，共注射七次，以确保持续暴露。进行了各种行为评估，包括旷场试验、埋大理石试验、悬尾试验、强迫游泳试验和蔗糖偏好试验，以评估焦虑和抑郁样行为。此外，我们测量了体重变化以及胸腺和肾上腺的相对重量，同时通过酶联免疫吸附测定（ELISA）对血清皮质酮和促肾上腺皮质激素水平进行了定量。利用FOSB（FBJ小鼠骨肉瘤病毒癌基因同源物B）免疫组织化学来评估应激相关脑区的慢性神经元激活。
结果表明，CUMS诱导抑郁样行为，这种反应受TRPA1状态的调节，并且当TRPA1通道功能正常时，DMTS处理可显著减轻这些影响。DMTS还减轻了由于下丘脑-垂体-肾上腺（HPA）轴失调导致的胸腺萎缩。
总体而言，DMTS似乎通过TRPA1介导的途径缓解抑郁和焦虑症状，表明其作为抑郁症和焦虑症的膳食补充剂或辅助治疗的潜力。
