Autophagic Impairment Contributes to Systemic Inflammation-Induced Dopaminergic Neuron Loss in the Midbrain |
| |
| Authors: | Hui-Fen Zheng Ya-Ping Yang Li-Fang Hu Mei-Xia Wang Fen Wang Li-Dan Cao Da Li Cheng-Jie Mao Kang-Ping Xiong Jian-Da Wang Chun-Feng Liu |
| |
| Institution: | 1. Department of Neurology, Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China.; 2. Institute of Neuroscience, Soochow University, Suzhou, Jiangsu, China.; 3. Department of Neurology, Yixing People’s Hospital, Yixing, Jiangsu, China.; Emory University, United States of America, |
| |
| Abstract: | BackgroundNeuroinflammation plays an important role in the pathogenesis of Parkinson’s disease (PD), inducing and accelerating dopaminergic (DA) neuron loss. Autophagy, a critical mechanism for clearing misfolded or aggregated proteins such as α-synuclein (α-SYN), may affect DA neuron survival in the midbrain. However, whether autophagy contributes to neuroinflammation-induced toxicity in DA neurons remains unknown.ResultsIntraperitoneal injection of lipopolysaccharide (LPS, 5 mg/kg) into young (3-month-old) and aged (16-month-old) male C57BL/6J mice was observed to cause persistent neuroinflammation that was associated with a delayed and progressive loss of DA neurons and accumulation of α-SYN in the midbrain. The autophagic substrate-p62 (SQSTM1) persistently increased, whereas LC3-II and HDAC6 exhibited early increases followed by a decline. In vitro studies further demonstrated that TNF-α induced cell death in PC12 cells. Moreover, a sublethal dose of TNF-α (50 ng/ml) increased the expression of LC3-II, p62, and α-SYN, implying that TNF-α triggered autophagic impairment in cells.ConclusionNeuroinflammation may cause autophagic impairment, which could in turn result in DA neuron degeneration in midbrain. |
| |
| Keywords: | |
|
|
