Developmental methylmercury (MeHg) exposures cause latent neurotoxic effects in adults; however, the mechanisms underlying the latent neurotoxicity are not fully understood. In the current study, we used C. elegans as an animal model to investigate the latent neurotoxic effects of developmental MeHg exposures on glutamatergic neurons. The young larvae stage 1 worms were exposed to MeHg (0.05 ~ 5 µM) for 48 h. The morphological and behavioral endpoints of glutamatergic neurons were compared when worms reached to adult stages including the young adult stage (day 1 adult) and the old adult stage (day 10 adult). Here, we showed that C. elegans glutamatergic neurons were morphologically intact following low or medium MeHg exposures (0.05 ~ 0.5 µM). The morphological damage of glutamatergic neurons appeared to be pronounced in day 10 adults developmentally exposed to 5 µM MeHg. Behavioral assays also showed an age-dependent latent effect of MeHg. In the nose touch response assay, only day 10 adult worms exhibited a functional decline following prior 5 µM MeHg exposure. Moreover, the disruption of NaCl memory appeared only in day 1 adults following MeHg exposures but not in day 10 adults. The expression of C. elegans homologs of mammalian vesicular glutamate transporter (eat-4) was repressed in day 1 adults, while the glutamate receptor homolog (glr-1) was upregulated in day 10 adults with 5 µM MeHg. In the comparison of age-dependent changes in the insulin-like pathway (daf-2/age-1/daf-16) following MeHg exposures, we showed that the daf-2/age-1/daf-16 pathway was mobilized in day 1 adults but repressed in day 10 adults. Collectively, our data supports a conclusion that MeHg-induced glutamatergic neurotoxicity exhibits an age-dependent pattern, possibly related to the prominent changes in age-dependent modulation in the glutamatergic neurotransmission and metabolic pathways.

发育期甲基汞 (MeHg) 暴露会对成人造成潜在的神经毒性影响；然而，潜在神经毒性的潜在机制尚不完全清楚。在当前的研究中，我们使用秀丽隐杆线虫作为动物模型来研究发育期甲基汞暴露对谷氨酸能神经元的潜在神经毒性影响。幼虫 1 期蠕虫暴露于甲基汞 (0.05 ~ 5 µM) 48 小时。当蠕虫达到成年阶段（包括年轻成年阶段（第 1 天成年）和老年阶段（第 10 天成年））时，比较谷氨酸能神经元的形态和行为终点。在这里，我们展示了秀丽隐杆线虫低或中等甲基汞暴露 (0.05 ~ 0.5 µM) 后，谷氨酸能神经元在形态上完好无损。谷氨酸能神经元的形态学损伤似乎在第 10 天成人发育暴露于 5 µM MeHg 时明显。行为分析也显示出甲基汞的年龄依赖性潜在影响。在鼻子触摸反应测定中，只有第 10 天的成年蠕虫在之前接触 5 µM MeHg 后表现出功能下降。此外，NaCl 记忆的破坏仅出现在接触甲基汞后第 1 天的成年人中，而第 10 天的成年人中则没有。哺乳动物囊泡谷氨酸转运蛋白 ( eat-4 ) 的秀丽隐杆线虫同系物的表达在第 1 天成虫中受到抑制，而谷氨酸受体同系物 ( glr-1)) 在 5 µM MeHg 的第 10 天成人中被上调。在比较甲基汞暴露后胰岛素样通路 ( daf-2/age-1/daf-16 ) 的年龄依赖性变化时，我们发现daf-2/age-1/daf-16通路在第 1 天的成年人，但在第 10 天的成年人中受到抑制。总的来说，我们的数据支持一个结论，即甲基汞诱导的谷氨酸能神经毒性表现出年龄依赖性模式，可能与谷氨酸能神经传递和代谢途径中年龄依赖性调节的显着变化有关。