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The NLRP3 Inflammasome is Involved in the Pathogenesis of Parkinson’s Disease in Rats
- Source :
- Neurochemical Research. 42:1104-1115
- Publication Year :
- 2017
- Publisher :
- Springer Science and Business Media LLC, 2017.
-
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.
- Subjects :
- Male
0301 basic medicine
Inflammasomes
Substantia nigra
Biology
Pharmacology
Biochemistry
Pyrin domain
Rats, Sprague-Dawley
Pathogenesis
Random Allocation
03 medical and health sciences
Cellular and Molecular Neuroscience
chemistry.chemical_compound
0302 clinical medicine
Parkinsonian Disorders
Dopamine
NLR Family, Pyrin Domain-Containing 3 Protein
medicine
Animals
Oxidopamine
Microinjection
Pars compacta
Inflammasome
General Medicine
Rats
030104 developmental biology
chemistry
Immunology
030217 neurology & neurosurgery
medicine.drug
Subjects
Details
- ISSN :
- 15736903 and 03643190
- Volume :
- 42
- Database :
- OpenAIRE
- Journal :
- Neurochemical Research
- Accession number :
- edsair.doi.dedup.....4c9aefc5ea5167b401e2e50af82d2860