Autophagic Impairment Contributes to Systemic Inflammation-induced Dopaminergic Neuron Loss in the Midbrain

Overview

Journal PLoS One

Specialties General Medicine
Science

Date 2013 Aug 13

PMID 23936437

Citations 20

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

Affiliations

Soon will be listed here.

Abstract

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 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.

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 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.

Conclusion: Neuroinflammation may cause autophagic impairment, which could in turn result in DA neuron degeneration in midbrain.

Citing Articles

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