Methylmercury (MeHg) is a potent neurotoxicant. The mechanisms underlying MeHg-induced neurotoxicity are not fully understood. Several studies have shown that protein chaperones are involved in MeHg toxicity. The protein co-chaperone, stress inducible protein 1 (STI-1), has important functions in protein quality control of the chaperone pathway. In the current study, dopaminergic (DAergic) cephalic (CEP) neuronal morphology was evaluated in the Caenorhabditis elegans (C. elegans) sti-1 knockout strain. In the control OH7193 strain (dat-1::mCherry + ttx-3::mCherry), we characterized the morphology of CEP neurons by checking the presence of attached vesicles and unattached vesicles to the CEP dendrites. We showed that the attached vesicles were only present in adult stage worms; whereas they were absent in the younger L3 stage worms. In the sti-1 knockout strain, MeHg treatment significantly altered the structures of CEP dendrites with discontinuation of mCherry fluorescence and shrinkage of CEP soma, as compared to the control. 12 h post treatment on MeHg-free OP50-seeded plates, the discontinuation of mCherry fluorescence of CEP dendrites in worms treated with 0.05 or 0.5 µM MeHg returned to levels statistically indistinguishable from control, while in worms treated with 5 µM MeHg a higher percentage of discontinuation of mCherry fluorescence persisted. Despite this strong effect by 5 µM MeHg, CEP attached vesicles were increased upon 0.05 or 0.5 µM MeHg treatment, yet unaffected by 5 µM MeHg. The CEP attached vesicles of sti-1 knockout strain were significantly increased shortly after MeHg treatment, but were unaffected 48 h post treatment. In addition, there was a significant interactive effect of MeHg and sti-1 on the number of attached vesicles. Knock down sti-1 via RNAi did not alter the number of CEP attached vesicles. Taking together, our data suggests that the increased occurrence of attached vesicles in adult stage worms could initiate a substantial loss of membrane components of CEP dendrites following release of vesicles, leading to the discontinuation of mCherry fluorescence, and the formation of CEP attached vesicles could be regulated by sti-1 to remove cellular debris for detoxification.

甲基汞 (MeHg) 是一种强效神经毒物。MeHg 诱导的神经毒性的机制尚不完全清楚。几项研究表明，蛋白质伴侣与甲基汞毒性有关。蛋白质共伴侣，应激诱导蛋白 1 (STI-1)，在伴侣途径的蛋白质质量控​​制中具有重要作用。在当前的研究中，对秀丽隐杆线虫( C. elegans ) sti-1中的多巴胺能 (DAergic) 头侧 (CEP) 神经元形态进行了评估淘汰赛应变。在对照 OH7193 菌株 (dat-1::mCherry + ttx-3::mCherry) 中，我们通过检查 CEP 树突上是否存在附着的囊泡和未附着的囊泡来表征 CEP 神经元的形态。我们发现附着的囊泡仅存在于成虫阶段。而在较年轻的 L3 阶段蠕虫中则不存在它们。在sti-1与对照相比，敲除菌株、MeHg 处理显着改变了 CEP 枝晶的结构，mCherry 荧光中断和 CEP 胞体收缩。在不含 MeHg 的 OP50 种子板上处理 12 小时后，用 0.05 或 0.5 µM MeHg 处理的蠕虫中 CEP 树突的 mCherry 荧光停止恢复到与对照在统计学上无法区分的水平，而在用 5 µM MeHg 处理的蠕虫中，更高百分比的mCherry 荧光的中断持续存在。尽管 5 µM MeHg 产生了强烈的影响，但 CEP 附着的囊泡在 0.05 或 0.5 µM MeHg 处理后增加，但不受 5 µM MeHg 的影响。sti-1的 CEP 附着囊泡敲除菌株在甲基汞处理后不久显着增加，但在处理后 48 小时不受影响。此外，MeHg 和sti-1对附着囊泡的数量有显着的交互作用。通过 RNAi敲低sti-1不会改变 CEP 附着囊泡的数量。综上所述，我们的数据表明，成虫期蠕虫附着囊泡的增加可能会在囊泡释放后引发 CEP 树突的膜成分大量损失，导致 mCherry 荧光中断，并且 CEP 附着囊泡的形成可能是受sti-1调节以去除细胞碎片以进行解毒。