Paraquat exposure induces Parkinsonism by altering lipid profile and evoking neuroinflammation in the midbrain

被引：27

作者：

Tong, Tong ^{[1
,2
]}

Duan, Weixia ^{[3
,4
]}

Xu, Yudong ^{[1
,2
]}

Hong, Huihui ^{[1
,2
]}

Xu, Jia ^{[1
,5
]}

Fu, Guanyan ^{[3
,4
]}

Wang, Xue ^{[6
]}

Yang, Lingling ^{[6
]}

Deng, Ping ^{[6
]}

Zhang, Jingjing ^{[1
,2
]}

He, Haotian ^{[1
,2
]}

Mao, Gaofeng ^{[7
]}

Lu, Yuanqiang ^{[1
,5
]}

Lin, Xiqin ^{[1
,2
]}

Yu, Zhengping ^{[6
]}

Pi, Huifeng ^{[6
]}

Cheng, Yong ^{[7
]}

Xu, Shangcheng ^{[3
,4
]}

Zhou, Zhou ^{[1
,2
,8
]}

机构：

[1] Zhejiang Univ, Affiliated Hosp 1, Sch Med, Dept Emergency Med, Hangzhou, Peoples R China

[2] Zhejiang Univ, Sch Med, Dept Environm Med, Hangzhou, Peoples R China

[3] Chongqing Prevent & Treatment Ctr Occupat Dis, Ctr Lab Med, Chongqing, Peoples R China

[4] Chongqing Key Lab Prevent & Treatment Occupat Dis, Chongqing, Peoples R China

[5] Zhejiang Prov Key Lab Diag & Treatment Aging & Phy, Hangzhou, Peoples R China

[6] Third Mil Med Univ, Dept Occupat Hlth, Chongqing, Peoples R China

[7] Gen Hosp Ctr Theater Command, Neurol Dept, Wuhan, Peoples R China

[8] Chongqing Univ, Ctr Neurointelligence, Sch Med, Chongqing, Peoples R China

来源：

ENVIRONMENT INTERNATIONAL | 2022年 / 169卷

基金：

中国国家自然科学基金;

关键词：

Paraquat; Parkinsonism; Lipidome; Inflammatory cytokines; Neuroinflammation; DISEASE; INFLAMMATION; RESOLUTION; MEDIATORS; ALPHA;

D O I：

10.1016/j.envint.2022.107512

中图分类号：

X [环境科学、安全科学];

学科分类号：

08 ; 0830 ;

摘要：

Paraquat (PQ) is the most widely used herbicide in the world and a well-known potent neurotoxin for humans. PQ exposure has been linked to increase the risk of Parkinson's disease (PD). However, the mechanism under-lying its neurotoxic effects in PD pathogenesis is unclear. In our present study, C57BL/6J mice treated with PQ manifested severe motor deficits indicated by the significant reductions in suspension score, latency to fall from rotarod, and grip strength at 8 weeks after PQ exposure. Pathological hallmarks of Parkinsonism in the midbrain such as dopaminergic neuron loss, increased alpha-synuclein protein, and dysregulated PD-related genes were observed. Non-targeted lipidome analysis demonstrated that PQ exposure alters lipid profile and abundance, increases pro-inflammatory lipids.27 significantly altered subclasses of lipids belonged to 6 different lipid cat-egories. Glycerophospholipids, sphingolipids, and glycerides were the most abundant lipids. Abundance of pro -inflammatory lipids such as Cer, LPC, LPS, and LPI was significantly increased in the midbrain. mRNA expres-sions of genes regulating ceramide biosynthesis in the midbrain were markedly up-regulated. Moreover, PQ exposure increased serum pro-inflammatory cytokines and provoked neuroinflammation in the midbrain. Pro -inflammatory lipids and cytokines in the midbrain were positively correlated with motor deficits. PQ poisoning in humans significantly also elevated serum pro-inflammatory cytokines and induced an intense systemic inflammation. In summary, we presented initial investigations of PQ induced molecular events related to the PD pathogenesis, capturing aspects of disturbed lipid metabolism, neuroinflammation, impairment of dopaminergic neurons in the midbrain, and an intense systemic inflammation. These neurotoxic effects of PQ exposure may mechanistically contribute to the pathogenesis of PQ induced Parkinsonism. Results of this study

引用

页数：15

共 1 条

[1] Chronic cadmium exposure induces Parkinson-like syndrome by eliciting sphingolipid disturbance and neuroinflammation in the midbrain of C57BL/6J mice
Xu, Yudong
Hong, Huihui
Lin, Xiqin
Tong, Tong
Zhang, Jingjing
He, Haotian
Yang, Lingling
Mao, Gaofeng
Hao, Rongrong
Deng, Ping
Yu, Zhengping
Pi, Huifeng
Cheng, Yong
Zhou, Zhou
ENVIRONMENTAL POLLUTION, 2023, 337

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