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The NLRP3 Inflammasome is Involved in the Pathogenesis of Parkinson’s Disease in Rats

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Abstract

The etiology and pathogenesis of Parkinson’s disease (PD) are complicated and have not been fully elucidated, but an important association has been identified between inflammation and PD. In this study, we investigated the role of the nucleotide-binding oligomerization domain, leucine rich repeat and pyrin domain-containing (NLRP) 3 inflammasome, consisting of NLRP3, caspase-1 and cytokines of the IL-1 family, in lipopolysaccharide (LPS)-induced and 6-hydroxydopamine (6-OHDA)-induced PD rats. Microinjection of different doses of caspase-1 inhibitor (Ac-YVAD-CMK, 300 or 1200 ng/rat) was performed for seven consecutive days. Then, rotational behavior, the number of dopamine (DA) neurons in the substantia nigra pars compacta (SNc), and the mRNA and protein expression levels of NLRP3 inflammasome components were measured 14 days after the microinjection setup was established. Results showed that high mRNA and protein expression levels of NLRP3 inflammasome components were observed in the injected side of the LPS- and 6-OHDA-induced PD rats; Ac-YVAD-CMK inhibited the mRNA and protein expression of NLRP3 inflammasome components in both LPS- and 6-OHDA-induced PD rats. Moreover, the number of rotations was significantly decreased, and the number of DA neurons in the SNc improved. Our data indicate that the NLRP3 inflammasome participates in the pathogenesis of PD and that inhibiting the downstream pathway of the NLRP3/caspase-1/IL-1β axis can alleviate the occurrence of PD symptoms, providing a new basis for the prevention and treatment of PD.

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Abbreviations

PD:

Parkinson’s disease

NLRP3:

Nucleotide-binding oligomerization domain, leucine rich repeat and pyrin domain-containing 3

LPS:

Lipopolysaccharide

6-OHDA:

6-Hydroxydopamine

DA:

Dopamine

TH:

Tyrosine hydroxylase

SNc:

Substantia nigra pars compacta

ASC:

Apoptosis-associated speck-like protein

MPTP:

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine

SD:

Sprague–Dawley

AP:

Anterior-posterior

ML:

Medial–lateral

DV:

Dorsal–ventral

ROS:

Reactive oxygen species

mtDNA:

Mitochondrial DNA

CNS:

Central nervous system

ICV:

Intracerebroventricular

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Acknowledgements

This study was supported by grants from the National Natural Science Foundation of China (Grant Number No. 30700244) and the Natural Science Foundation of Hubei Province (Grant Number 2012FFB02501).

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Authors and Affiliations

  1. Department of Neurology, Tongji Hospital, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan, Hubei, 430030, China

    Zhijuan Mao, Chanchan Liu, Suqiong Ji, Qingmei Yang, Hongxiang Ye & Zheng Xue

  2. Department of Neurology, Guangzhou First People’s Hospital, Guangzhou Medical University, Guangzhou, Guangdong Province, China

    Haiyan Han

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  1. Zhijuan Mao
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Mao, Z., Liu, C., Ji, S. et al. The NLRP3 Inflammasome is Involved in the Pathogenesis of Parkinson’s Disease in Rats. Neurochem Res 42, 1104–1115 (2017). https://doi.org/10.1007/s11064-017-2185-0

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