Aging-related motor function and dopaminergic neuronal loss in C57BL/6 mice
Aging-related motor function and dopaminergic neuronal loss in C57BL/6 mice
复制标题
DOI：
10.1186/s13041-020-00585-6
复制
发表时间：
2020-03-23
期刊：
影响因子：
3.6
通讯作者：
Hattori, Nobutaka
中科院分区：
文献类型：
--
作者：
Noda, Sachiko;Sato, Shigeto;Hattori, Nobutaka
衰老相关的多巴胺能神经元损失及其运动表型是众所周知的。多巴胺能神经元的过度损失导致帕金森病（PD），这是最常见的神经退行性疾病，其特征在于黑质纹状体多巴胺产生神经元的损失。然而，在小鼠中，与衰老相关的多巴胺能神经元损失及其对运动功能的后果知之甚少。我们观察了野生型C57 BL/6小鼠的表型在一段延长的时间。C57 BL/6小鼠表现出年龄依赖性运动障碍，包括后肢缺陷和老年小鼠多巴胺能神经元数量减少，导致运动功能障碍。我们使用高效液相色谱法（HPLC）观察到老年小鼠纹状体多巴胺水平降低。因此，多巴胺水平受到多巴胺能神经元损失的影响。此外，破碎的线粒体中观察到的多巴胺能神经元的老年小鼠，而不是在年轻的小鼠。衰老相关的多巴胺能神经元损失和受损线粒体的积累可能是衰老的病理生理学基础。
Aging-related dopaminergic neuronal loss and its motor phenotypes are well known. Excessive loss of dopaminergic neurons leads to Parkinson's disease (PD), the most common neurodegenerative disorder characterized by the loss of nigrostriatal dopamine-producing neurons. In mice, however, aging-related dopaminergic neuronal loss and its consequences for motor function are poorly understood. We observed the phenotype of wild-type C57BL/6 mice over an extended period of time. C57BL/6 mice exhibited age-dependent locomotor impairments, including hindlimb defects and the number of dopaminergic neurons decreased in aged mice, contributing to locomotor dysfunction. We observed a reduction in striatal dopamine levels in aged mice using high-performance liquid chromatography (HPLC). Thus, dopamine levels are affected by the loss of dopaminergic neurons. Furthermore, fragmented mitochondria were observed in dopaminergic neurons of aged mice but not in those of young mice. Aging-related dopaminergic neuronal loss and accumulation of damaged mitochondria may underlie the pathophysiology of aging.