Bouabid Safa, Fifel Karim, Benazzouz Abdelhamid, Lakhdar-Ghazal Nouria
University Mohamed V, Faculty of Sciences, Unit of Research on Biological Rhythms and Environment, Rabat, Morocco.
Laboratory of Neurophysiology, Molecular Cell Biology Department, Leiden University Medical Center, PO Box 9600 Mailbox S5-P, 2300 RC Leiden, The Netherlands.
Neuroscience. 2016 Sep 7;331:13-23. doi: 10.1016/j.neuroscience.2016.06.016. Epub 2016 Jun 15.
Manganese (Mn) intoxication is associated with neurological dysfunctions collectively known as Parkinsonism or Manganism. Like in Parkinson's disease, Manganism is associated with motor disturbances, together with non-motor symptoms including cognitive and neuropsychiatric deficits. Although sleep dysfunctions are commonly reported among workers exposed to Mn, their underlying pathophysiology remains unknown. In this study, we investigated the rest-activity rhythms in rats treated daily with MnCl2 (10mg/kg, i.p) for 5weeks. Locomotor activity was assessed under a light-dark (LD) cycle, constant darkness (DD) and during adjustment to 6h shifts of the LD cycle. In LD conditions, Mn-treated rats exhibited a more fragmented and less stable rest-activity rhythm in addition to a reduction in the total 24-h amount of locomotor activity as well as in the activity confined to the active dark phase of the LD. Consequently, a significant decrease in the amplitude of the rest-activity rhythm was observed. These disturbances were displayed during and after Mn treatment. Furthermore, after the 6-h phase advance of the LD cycle, Mn-treated rats failed to re-adjust accurately their behavioral activity to the new shifted LD cycle. Upon release from LD into DD, Mn-treated rats expressed a normal and stable free-running period of their rest-activity rhythm (23.92±0.07h in Mn group vs. 24.01±0.04h in control rats). However, their rest-activity rhythm remained highly fragmented and less stable. Our results provide the first evidence that chronic Mn intoxication leads to impairment of rest-activity rhythms in addition to the motor and non-motor disturbances reported in Manganism.
锰（Mn）中毒与统称为帕金森症或锰中毒的神经功能障碍有关。与帕金森病一样，锰中毒与运动障碍有关，同时还伴有包括认知和神经精神缺陷在内的非运动症状。尽管在接触锰的工人中普遍报告存在睡眠功能障碍，但其潜在的病理生理学仍不清楚。在本研究中，我们调查了每天腹腔注射MnCl2（10mg/kg）持续5周的大鼠的静息-活动节律。在明暗（LD）循环、持续黑暗（DD）条件下以及在适应LD循环6小时的转换过程中评估运动活动。在LD条件下，除了24小时总运动活动量减少以及局限于LD活跃暗期的活动减少外，经锰处理的大鼠还表现出更碎片化且更不稳定的静息-活动节律。因此，观察到静息-活动节律的振幅显著降低。这些干扰在锰处理期间和之后都有表现。此外，在LD循环提前6小时后，经锰处理的大鼠未能准确地将其行为活动重新调整到新的转换后的LD循环。从LD释放到DD后，经锰处理的大鼠表现出其静息-活动节律的正常且稳定的自由运行周期（锰组为23.92±0.07小时，对照组大鼠为24.01±0.04小时）。然而，它们的静息-活动节律仍然高度碎片化且不太稳定。我们的结果提供了首个证据，即慢性锰中毒除了导致锰中毒中报告的运动和非运动干扰外，还会导致静息-活动节律受损。
