Noda Sachiko, Sato Shigeto, Fukuda Takahiro, Tada Norihiro, Hattori Nobutaka
Department of Neurology, Juntendo University Graduate School of Medicine, Tokyo, 113-8421, Japan.
Division of Neuropathology, Department of Neuropathology, The Jikei University, School of Medicine, Tokyo, 105-8461, Japan.
Mol Brain. 2020 Mar 23;13(1):46. doi: 10.1186/s13041-020-00585-6.
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.
衰老相关的多巴胺能神经元丢失及其运动表型是众所周知的。多巴胺能神经元的过度丢失会导致帕金森病(PD),这是最常见的神经退行性疾病,其特征是黑质纹状体中产生多巴胺的神经元丢失。然而,在小鼠中,衰老相关的多巴胺能神经元丢失及其对运动功能的影响却知之甚少。我们在较长一段时间内观察了野生型C57BL/6小鼠的表型。C57BL/6小鼠表现出年龄依赖性的运动障碍,包括后肢缺陷,并且老年小鼠中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,多巴胺水平受多巴胺能神经元丢失的影响。此外,在老年小鼠的多巴胺能神经元中观察到线粒体碎片化,但在年轻小鼠中未观察到。衰老相关的多巴胺能神经元丢失和受损线粒体的积累可能是衰老病理生理学的基础。