Laboratory of Biological Membranes, Faculty of Biology, Lomonosov Moscow State University, 119991 Moscow, Russia.
Department of Higher Nervous Activity, Faculty of Biology, Lomonosov Moscow State University, 119991 Moscow, Russia; Laboratory of Experimental and Translational Neurochemistry, Research Center of Neurology, Volokolamskoe Shosse, 80, Moscow 125367, Russia.
Neurotoxicology. 2023 Sep;98:86-97. doi: 10.1016/j.neuro.2023.08.002. Epub 2023 Aug 19.
Overexposure to Mn causes a neurological disorder-manganism-with motor symptoms that overlap closely with disorders associated with haploinsufficiency in the gene encoding for α isoform of Na,K-ATPase (NKA). The present study was designed to test the hypothesis that behavioral changes in the mouse model of manganism may be associated with changes in the expression and activity of α NKA in the cerebellum (CB) and striatum (STR)-the key brain structures responsible for motor control in adult mice. C57Bl/6 mice were exposed to MnCl at 0.5 g/L (in drinking water) for up to eight weeks. After four weeks of Mn consumption, Mn levels were increased in the CB only. Behavioral tests demonstrated decreased performance of Mn-treated mice in the shuttle box test (third through sixth weeks), and the inclined grid walking test (first through sixth weeks), suggesting the development of learning impairment, decreased locomotion, and motor discoordination. The activity of NKA significantly decreased, and the expression of α1-α3 isoforms of NKA increased in the second week in the CB only. Thus, signs of learning and motor disturbances developing in this model of manganism are unlikely to be directly linked to disturbances in the expression or activity of NKA in the CB or STR. Whether these early changes may contribute to the pathogenesis of later behavioral deficits remains to be determined.
过量的锰会导致一种神经紊乱——锰中毒，其运动症状与编码α同工型钠钾-ATP 酶（NKA）的基因单倍不足相关的疾病非常相似。本研究旨在验证一个假设，即锰中毒小鼠模型中的行为变化可能与小脑 (CB) 和纹状体 (STR) 中 NKA 的表达和活性变化有关，小脑和纹状体是成年小鼠运动控制的关键脑结构。C57Bl/6 小鼠被暴露于 0.5g/L 的 MnCl（在饮用水中）长达八周。在锰摄入四周后，仅在 CB 中增加了 Mn 水平。行为测试表明，接受 Mn 处理的小鼠在穿梭箱测试（第三至第六周）和斜网格行走测试（第一至第六周）中的表现下降，这表明学习障碍、运动减少和运动协调障碍的发展。仅在第二周，NKA 的活性显著降低，NKA 的α1-α3 同工型的表达增加。因此，在这种锰中毒模型中出现的学习和运动障碍的迹象不太可能与 CB 或 STR 中 NKA 的表达或活性的紊乱直接相关。这些早期变化是否可能导致以后的行为缺陷，仍有待确定。
