机构：[1]Key Laboratory of Neural Regeneration and Repair, Department of Neurobiology, Capital Medical University, 10 Xi Tou Tiao, You Anmen, Beijing 100069, China[2]Department of Neurobiology, Xuanwu Hospital, Capital Medical University, Beijing, China首都医科大学宣武医院[3]Center for Parkinson’s Disease Beijing Institute for Brain Disorders, Key Laboratory for Neurodegenerative Diseases of the Ministry of Education, Beijing, China
Aberrant alpha-synuclein (alpha-syn) accumulation has been shown to impair mitochondrial function by reducing mitochondrial membrane potential (MMP). However, the underlying mechanisms remain elusive. Transient receptor potential canonical (TRPC) channels are a diverse group of non-selective Ca2+ channels, among which TRPC3 is the only one that is localized in mitochondria and plays a role in maintaining the normal MMP. This raises a possibility that altered TRPC3 expression may play a role in the mitochondrial dysfunction induced by alpha-syn accumulation. To demonstrate this possibility, we first examined the expressions of mitochondrial TRPC3 in the brains of aging monkeys and alpha-syn transgenic and wild-type mice. We showed that alpha-syn levels increased in mitochondria in an age-dependent manner that was positively correlated to an elevation of mitochondrial TRPC3. This correlation was more prominent in the striatum than in the cerebellum, possibly due to the greater age-dependent alpha-syn accumulation in the striatum than in the cerebellum. We then used primary neurons overexpressing alpha-syn to investigate the effect of the alpha-syn-induced elevation of mitochondrial TRPC3 on the MMP and apoptotic cell death. We found that neurons with overexpressed alpha-syn had increased mitochondrial TRPC3 and decreased MMP, which were accompanied by increased number of apoptotic neurons. Suppressing TRPC3 expression partially reversed the reduction of MMP and alleviated the apoptotic cell death, indicating that the mitochondrial TRPC3 may play a role in the mitochondrial dysfunction in neurons with alpha-syn accumulation that may occur in not only the aged brain but also the brain with PD.
基金：
National Key Research and Development Plan of China (Grant No. 2016YFC1306000);
National Natural Science Foundation of China (Grant No. 81371398, 81371200);
the Natural Science Foundation of Beijing (Grant No. 7131001);
the Project of Construction of Innovative Teams and Teacher Career Development for Universities and Colleges under Beijing Municipality (IDHT20140514).
第一作者机构：[1]Key Laboratory of Neural Regeneration and Repair, Department of Neurobiology, Capital Medical University, 10 Xi Tou Tiao, You Anmen, Beijing 100069, China[3]Center for Parkinson’s Disease Beijing Institute for Brain Disorders, Key Laboratory for Neurodegenerative Diseases of the Ministry of Education, Beijing, China
通讯作者：
通讯机构：[1]Key Laboratory of Neural Regeneration and Repair, Department of Neurobiology, Capital Medical University, 10 Xi Tou Tiao, You Anmen, Beijing 100069, China[2]Department of Neurobiology, Xuanwu Hospital, Capital Medical University, Beijing, China[3]Center for Parkinson’s Disease Beijing Institute for Brain Disorders, Key Laboratory for Neurodegenerative Diseases of the Ministry of Education, Beijing, China
推荐引用方式(GB/T 7714)：
Min Chen,Jia Liu,Yongquan Lu,et al.Age-dependent alpha-synuclein accumulation is correlated with elevation of mitochondrial TRPC3 in the brains of monkeys and mice[J].JOURNAL OF NEURAL TRANSMISSION.2017,124(4):441-453.doi:10.1007/s00702-016-1654-y.
APA：
Min Chen,Jia Liu,Yongquan Lu,Chunli Duan,Lingling Lu...&Hui Yang.(2017).Age-dependent alpha-synuclein accumulation is correlated with elevation of mitochondrial TRPC3 in the brains of monkeys and mice.JOURNAL OF NEURAL TRANSMISSION,124,(4)
MLA：
Min Chen,et al."Age-dependent alpha-synuclein accumulation is correlated with elevation of mitochondrial TRPC3 in the brains of monkeys and mice".JOURNAL OF NEURAL TRANSMISSION 124..4(2017):441-453
