机构：[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
Background: Neuroinflammation 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 alpha-synuclein (alpha-SYN), may affect DA neuron survival in the midbrain. However, whether autophagy contributes to neuroinflammation-induced toxicity in DA neurons remains unknown. Results: Intraperitoneal 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 alpha-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-alpha induced cell death in PC12 cells. Moreover, a sublethal dose of TNF-alpha (50 ng/ml) increased the expression of LC3-II, p62, and alpha-SYN, implying that TNF-alpha triggered autophagic impairment in cells. Conclusion: Neuroinflammation may cause autophagic impairment, which could in turn result in DA neuron degeneration in midbrain.
基金：
This work was supported by grants from National Natural Science Foundation of China (81171213 to LCF and 81171212 to HLF), Natural Science
Foundation of Jiangsu Province of China (BK2010228to LCF). This work was also partially supported by the National Basic Science Key Project (973 project,
2011CB510003).
第一作者机构：[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
共同第一作者：
通讯作者：
通讯机构：[1]Department of Neurology, Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China,[2]Institute of Neuroscience, Soochow University, Suzhou, Jiangsu, China,
推荐引用方式(GB/T 7714)：
Hui-Fen Zheng,Ya-Ping Yang,Li-Fang Hu,et al.Autophagic Impairment Contributes to Systemic Inflammation-Induced Dopaminergic Neuron Loss in the Midbrain[J].PLOS ONE.2013,8(8):e70472.doi:10.1371/journal.pone.0070472.
APA：
Hui-Fen Zheng,Ya-Ping Yang,Li-Fang Hu,Mei-Xia Wang,Fen Wang...&Chun-Feng Liu.(2013).Autophagic Impairment Contributes to Systemic Inflammation-Induced Dopaminergic Neuron Loss in the Midbrain.PLOS ONE,8,(8)
MLA：
Hui-Fen Zheng,et al."Autophagic Impairment Contributes to Systemic Inflammation-Induced Dopaminergic Neuron Loss in the Midbrain".PLOS ONE 8..8(2013):e70472
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