Tropical Journal of Pharmaceutical Research

Original Research Article | OPEN ACCESS

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

Xuqing Cao¹, Jiangtao Guo² , Hidek Mochizuki³, Zhimin Shi⁴, Peilan Zhang⁵, Zhimei Liu⁴, Tao Zhang⁴, Jinxi Qi⁴, Dong Xu⁴

¹Department of Neurology, People's Hospital of Ningxia Hui Autonomous Region (The Affiliated People's Hospital of Ningxia Medical University and The First Affiliated Hospital of Northwest Minzu University), Yinchuan 750002; ²Department of Rheumatogy and Immunology, People's Hospital of Ningxia Hui Autonomous Region (The Affiliated People's Hospital of Ningxia Medical University and The First Affiliated Hospital of Northwest Minzu University), Yinchuan 750002, China; ³Department of Neurology, Osaka University Graduate School of Medicine, Osaka, Japan; ⁴Department of Neurology, People’s Hospital of Ningxia Hui Autonomous Region, Yinchuan 750002; ⁵Department of Neurology, Tianjin Huanhu Hospital, Tianjin 300350, PR China.

For correspondence:- Jiangtao Guo Email: ckha04@163.com

Accepted: 17 May 2021 Published: 30 June 2021

Citation: Cao X, Guo J, Mochizuki H, Shi Z, Zhang P, Liu Z, et al. Regulatory mechanism of miR-146a on MPTP-induced neuroinflammation in mice with Parkinson's disease. Trop J Pharm Res 2021; 20(6):1139-1144 doi: 10.4314/tjpr.v20i6.6

© 2021 The authors.
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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.

Keywords: Inflammatory cytokines, IRAKI-1, MicroRNA-146a, Neuroinflammation, Parkinson's disease