Department of Occupational and Environmental Health, School of Public Health, Fourth Military Medical University, Xi'an 710032, PR China.
Environ Toxicol Pharmacol. 2011 Jan;31(1):171-8. doi: 10.1016/j.etap.2010.10.004. Epub 2010 Oct 23.
Our previous studies showed chronic exposure to manganese chloride (Mn) causes locomotor impairment and lesion of dopaminergic neurons in substantia nigra (SN). But effects of acute Mn exposure on locomotor ability, SN dopaminergic and GABAergic neurons were not clear. In the current study, Mn was injected into the striatum of GAD(67)-GFP mice. Twenty-four hours after injection, locomotor ability was quantitatively evaluated with behavioral tests (rotarod test and open field test). Meanwhile, the numbers of dopaminergic and GABAergic neurons were counted through immunofluorescent staining for TH and GFP respectively, and activations of dopaminergic and GABAergic neurons were evaluated by double immunofluorescent labeling for TH/Fos and GFP/Fos, respectively. Behavioral tests showed a significant locomotor impairment 24h after Mn injection. The numbers of SN dopaminergic and GABAergic neurons were not altered significantly 24h after Mn injection; however, some of SN GABAergic neurons were activated and dopaminergic neurons were left inactivated. In addition, there were still a large number of Mn-activated neurons that fell into neither dopaminergic nor GABAergic criteria. Our data suggested that activation of SN GABAergic neurons but not lesion of dopaminergic neurons, which was found to play an important role in the Mn-induced chronic neurotoxicity in our previous studies, contributed partially to Mn-induced acute locomotor impairment. Therefore we come to the conclusion that Mn exposure can induce acute or chronic neurotoxicity via different neuronal elements.
我们之前的研究表明，慢性暴露于氯化锰（Mn）会导致运动障碍和黑质（SN）多巴胺能神经元的损伤。但是，急性 Mn 暴露对运动能力、SN 多巴胺能和 GABA 能神经元的影响尚不清楚。在本研究中，Mn 被注射到 GAD(67)-GFP 小鼠的纹状体中。注射后 24 小时，通过行为测试（转棒测试和旷场测试）定量评估运动能力。同时，通过 TH 和 GFP 的免疫荧光染色分别计数多巴胺能和 GABA 能神经元的数量，并通过 TH/Fos 和 GFP/Fos 的双重免疫荧光标记分别评估多巴胺能和 GABA 能神经元的激活。行为测试显示，Mn 注射后 24 小时运动能力明显受损。Mn 注射后 24 小时 SN 多巴胺能和 GABA 能神经元的数量没有明显改变；然而，一些 SN GABA 能神经元被激活，而多巴胺能神经元未被激活。此外，仍有大量 Mn 激活的神经元既不属于多巴胺能神经元，也不属于 GABA 能神经元。我们的数据表明，SN GABA 能神经元的激活，而不是多巴胺能神经元的损伤，这在我们之前的研究中被发现对 Mn 诱导的慢性神经毒性起着重要作用，部分导致了 Mn 诱导的急性运动障碍。因此，我们得出结论，Mn 暴露可以通过不同的神经元成分引起急性或慢性神经毒性。
