Department of Neurobiology School of Basic Medical Sciences, Key Laboratory of Neural Regeneration and Repair, Center for Parkinson's Disease, Key Laboratory for Neurodegenerative Diseases of the Ministry of Education, Beijing Institute for Brain Disorders, Capital Medical University, Beijing, China.
Guangxi Neurological Disease Clinical Research Center, Laboratory of Neuroscience, Affiliated Hospital of Guilin Medical University, Guilin, China.
J Cell Mol Med. 2022 Oct;26(19):5008-5020. doi: 10.1111/jcmm.17524. Epub 2022 Aug 27.
Olfactory impairment is an initial non-motor symptom of Parkinson's disease that causes the deposition of aggregated α-synuclein (α-syn) in olfactory neurons. Transient receptor potential canonical (TRPC) channels are a diverse group of non-selective Ca entry channels involved in the progression or pathogenesis of PD via Ca homeostatic regulation. However, the relationship between TRPC and α-syn pathology in an olfactory system remains unclear. To address this issue, we assessed the olfactory function in α-syn transgenic mice. In contrast with control mice, the transgenic mice exhibited impaired olfaction, TRPC3 activation and apoptotic neuronal cell death in the olfactory system. Similar results were observed in primary cultures of olfactory neurons, that is TRPC3 activation, increasing intracellular Ca concentration and apoptotic cell death in the α-syn-overexpressed neurons. These changes were significantly attenuated by TRPC3 knockdown. Therefore, our findings suggest that TRPC3 activation and calcium dyshomeostasis play a key role in α-syn-induced olfactory dysfunction in mice.
嗅觉障碍是帕金森病的初始非运动症状，导致聚集的α-突触核蛋白（α-syn）在嗅觉神经元中沉积。瞬时受体电位经典（TRPC）通道是一组多样化的非选择性钙进入通道，通过钙动态平衡调节参与 PD 的进展或发病机制。然而，TRPC 与嗅觉系统中 α-syn 病理学之间的关系尚不清楚。为了解决这个问题，我们评估了α-syn 转基因小鼠的嗅觉功能。与对照组小鼠相比，转基因小鼠表现出嗅觉功能障碍、TRPC3 激活和嗅觉系统中神经元细胞凋亡。在嗅觉神经元的原代培养中也观察到了类似的结果，即α-syn 过表达神经元中 TRPC3 激活、细胞内 Ca 浓度增加和细胞凋亡。TRPC3 敲低显著减弱了这些变化。因此，我们的研究结果表明，TRPC3 激活和钙动态平衡失调在α-syn 诱导的小鼠嗅觉功能障碍中起关键作用。
