PDF(Pubmed)
Abstract：
Polysulfides are endogenously produced in mammals and generally associated with protective functions. Our aim was to investigate the effect of dimethyl trisulfide (DMTS) in a mouse model of acute stress. DMTS activates transient receptor potential ankyrin 1 (TRPA1) channels and leads to neuropeptide release, potentially that of substance P (SP). We hypothesize that DMTS might inhibit the degrading enzymes of endocannabinoids, so this system was also investigated as another possible pathway for mediating the effects of DMTS. Trpa1 gene wild-type (WT) and knockout (KO) mice were used to confirm the role of the TRPA1 ion channel in mediating the effects of DMTS. C57BL/6J, NK1 gene KO, and Tac1 gene KO mice were used to evaluate the effect of DMTS on the release and expression of SP. Some C57BL/6J animals were treated with AM251, an inhibitor of the cannabinoid CB1 receptor, to elucidate the role of the endocannabinoid system in these processes. Open field test (OFT) and forced swim test (FST) were performed in each mouse strain. A tail suspension test (TST) was performed in Trpa1 WT and KO animals. C-FOS immunohistochemistry was carried out on Trpa1 WT and KO animals. The DMTS treatment increased the number of highly active periods and decreased immobility time in the FST in WT animals, but had no effect on the Trpa1 KO mice. The DMTS administration induced neuronal activation in the Trpa1 WT mice in the stress-related brain areas, such as the locus coeruleus, dorsal raphe nucleus, lateral septum, paraventricular nucleus of the thalamus, and paraventricular nucleus of the hypothalamus. DMTS may have a potential role in the regulation of stress-related processes, and the TRPA1 ion channel may also be involved in mediating the effects of DMTS. DMTS can be an ideal candidate for further study as a potential remedy for stress-related disorders.
摘要：
多硫化物在哺乳动物中内源性产生并且通常与保护功能相关。我们的目的是研究二甲基三硫（DMTS）在急性应激小鼠模型中的作用。DMTS激活瞬时受体电位锚蛋白1（TRPA1）通道并导致神经肽释放，潜在的P物质(SP)。我们假设DMTS可能会抑制内源性大麻素的降解酶，因此，该系统也作为介导DMTS效应的另一个可能途径进行了研究。使用Trpa1基因野生型（WT）和敲除（KO）小鼠来确认TRPA1离子通道在介导DMTS作用中的作用。C57BL/6J,NK1基因KO,用Tac1基因KO小鼠评价DMTS对SP释放和表达的影响。一些C57BL/6J动物用大麻素CB1受体抑制剂AM251治疗，阐明内源性大麻素系统在这些过程中的作用。在每个小鼠品系中进行开场测试(OFT)和强迫游泳测试(FST)。在Trpa1WT和KO动物中进行尾部悬吊试验(TST)。在Trpa1WT和KO动物上进行C-FOS免疫组织化学。DMTS治疗增加了WT动物FST中高度活跃期的数量并减少了不动时间，但对Trpa1KO小鼠没有影响。DMTS给药诱导Trpa1WT小鼠应激相关脑区的神经元激活,比如蓝斑，中缝背侧核,外侧隔,丘脑室旁核,下丘脑室旁核.DMTS可能在压力相关过程的调节中发挥潜在作用，TRPA1离子通道也可能参与介导DMTS的作用。DMTS可能是进一步研究的理想候选者，可作为压力相关疾病的潜在补救措施。
