Regulatory mechanism of miR-146a on MPTP-induced neuroinflammation in mice with Parkinson's disease

Abstract

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.