Open AccessRegulatory mechanism of miR-146a on MPTP-induced neuroinflammation in mice with Parkinson's disease
Author(s) -
Xuqing Cao,
Jiangtao Guo,
Hidek Mochizuki,
Zhimin Shi,
Peilan Zhang,
Zhimei Liu,
Tao Zhang,
Jinxi Qi,
Danyan Xu
Publication year - 2022
Publication title -
tropical journal of pharmaceutical research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.209
H-Index - 36
eISSN - 1596-5996
pISSN - 1596-9827
DOI - 10.4314/tjpr.v20i6.6
Subject(s) - neuroinflammation , mptp , downregulation and upregulation , interleukin 6 , messenger rna , tumor necrosis factor alpha , parkinson's disease , pathogenesis , receptor , endocrinology , real time polymerase chain reaction , medicine , chemistry , microbiology and biotechnology , biology , disease , cytokine , gene , biochemistry
Purpose: To study the regulatory influence of microRNA-146a (miR-146a) on 1-methyl-4-phenyl-1,2,3, 6-tetrahydropyridine (MPTP)-induced neuroinflammation in mice with Parkinson's disease (PD).
Methods: Forty specific pathogen-free (SPF) male C57BL/6 mice were divided into 2 groups: normal control and PD groups. The 2 groups were each divided into 2 subgroups: miR-146a inhibitor and inhibitor control groups. The mRNA and protein expressions of miR-146a, interleukin-1 receptor- associated kinase-1 (IRAK-1) and P65-NF-κB were determined by quantitative real-time polymerase chain reaction (qRT-PCR) and immunoblot assay, respectively. Levels of interleukin (IL)-1, IL-6 and TNF-α were assayed by enzyme-linked immunosorbent assay (ELISA).
Results: The level of expression of miR-146a was significantly and time-dependently increased in PD mice, relative to control (p < 0.05). In PD group, mRNA and protein expressions of IRAK-1 were markedly higher in miR-146a inhibitor group than in inhibitor control (p < 0.05). Protein expression of P65-NF-κB was significantly upregulated in brains of PD mice, relative to normal mice (p < 0.05). Moreover, IL-1, IL-6 and TNF-α levels were significantly higher in brains of PD mice than in control.
Conclusion: These results show the involvement of miR-146a in the etiology of PD, and that its regulation of neuroinflammation occurs via inhibition of IRAK1 gene expression. This finding may be useful in the development of new anti-PD drugs based on miR-146a.