1. Academic Validation
  2. MicroRNA-155-5p promotes neuroinflammation and central sensitization via inhibiting SIRT1 in a nitroglycerin-induced chronic migraine mouse model

MicroRNA-155-5p promotes neuroinflammation and central sensitization via inhibiting SIRT1 in a nitroglycerin-induced chronic migraine mouse model

  • J Neuroinflammation. 2021 Dec 10;18(1):287. doi: 10.1186/s12974-021-02342-5.
Qianwen Wen 1 Yunfeng Wang 2 3 Qi Pan 2 Ruimin Tian 2 Dunke Zhang 1 Guangcheng Qin 1 Jiying Zhou 2 Lixue Chen 4
Affiliations

Affiliations

  • 1 Laboratory Research Center, The First Affiliated Hospital of Chongqing Medical University, 1st You Yi Road, Yu Zhong, Chongqing, 400016, China.
  • 2 Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
  • 3 Department of Neurology, Nanchong Central Hospital, Nanchong, China.
  • 4 Laboratory Research Center, The First Affiliated Hospital of Chongqing Medical University, 1st You Yi Road, Yu Zhong, Chongqing, 400016, China. chenlixue@hospital.cqmu.edu.cn.
Abstract

Background: Previous studies have confirmed that the microglial activation and subsequent inflammatory responses in the trigeminal nucleus caudalis (TNC) are involved in the central sensitization of chronic migraine (CM). MicroRNA-155-5p has been shown to modulate the polarization of microglia and participate in inflammatory processes in a variety of neurological diseases. However, its role in CM remains unclear. The purpose of this study was to determine the precise role of miR-155-5p in CM.

Methods: A model of CM in C57BL/6 mice was established by recurrent intraperitoneal injection of nitroglycerin (NTG). Mechanical and thermal hyperalgesia were evaluated by Von Frey filaments and radiant heat. The expression of miR-155-5p was examined by qRT-PCR, and the mRNA and protein levels of silent information regulator 1(SIRT1) were measured by qRT-PCR, Western blotting (WB) and immunofluorescence (IF) analysis. The miR-155-5p antagomir, miR-155-5p agomir, SRT1720 (a SIRT1 Activator) and EX527 (a SIRT1 Inhibitor) were administered to confirm the effects of miR-155-5p and SIRT1 on neuroinflammation and the central sensitization of CM. ELISA, WB and IF assays were applied to evaluate the expression of TNF-α, myeloperoxidase (MPO), IL-10, p-ERK, p-CREB, Calcitonin gene-related peptide (CGRP), c-Fos and microglial activation. The cellular localization of SIRT1 was illustrated by IF.

Results: After the NTG-induced mouse model of CM was established, the expression of miR-155-5p was increased. The level of SIRT1 was decreased, and partly colocalized with Iba1 in the TNC. The miR-155-5p antagomir and SRT1720 downregulated the expression of p-ERK, p-CREB, CGRP, and c-Fos, alleviating microglial activation and decreasing inflammatory substances (TNF-α, MPO). The administration of miR-155-5p agomir or EX527 exacerbated neuroinflammation and central sensitization. Importantly, the miR-155-5p agomir elevated CGRP and c-Fos expression and microglial activation, which could subsequently be alleviated by SRT1720.

Conclusions: These data demonstrate that upregulated miR-155-5p in the TNC participates in the central sensitization of CM. Inhibiting miR-155-5p alleviates neuroinflammation by activating SIRT1 in the TNC of CM mice.

Keywords

Central sensitization; Chronic migraine; Inflammation; MiR-155-5p; Microglia; SIRT1.

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