Suppression of miR-155 attenuates neuropathic pain by inducing an M1 to M2 switch in microglia

Zhang, Yanxiang; Chen, Qi; Nai, Yu; Cao, Chunni

doi:10.5114/fn.2020.94008

Cited by 19 publications

(11 citation statements)

References 50 publications

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“…On the one hand, miR-155 is linked to T cell dysregulation [ 87 ], another important feature of AD pathophysiology. Additionally, the suppression of miR-155 was demonstrated to promote the microglial switch from the M1 pro-inflammatory phenotype to the neuroprotective M2 phenotype [ 88 ]. On the other hand, data from earlier studies conducted on AD animal models might be confusing as the inhibition of miR-155 expression was shown to be correlated to increased Aβ plaque level at the cerebral level [ 56 ].…”

Section: Related Mechanisms and Future Research Directionsmentioning

confidence: 99%

The Role of Human Herpesvirus 6 Infection in Alzheimer’s Disease Pathogenicity—A Theoretical Mosaic

Romanescu

Schreiner

Mukovozov

2022

JCM

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Alzheimer’s disease (AD), a neurodegenerative disorder generally affecting older adults, is the most common form of dementia worldwide. The disease is marked by severe cognitive and psychiatric decline and has dramatic personal and social consequences. Considerable time and resources are dedicated to the pursuit of a better understanding of disease mechanisms; however, the ultimate goal of obtaining a viable treatment option remains elusive. Neurodegenerative disease as an outcome of gene–environment interaction is a notion widely accepted today; a clear understanding of how external factors are involved in disease pathogenesis is missing, however. In the case of AD, significant effort has been invested in the study of viral pathogens and their role in disease mechanisms. The current scoping review focuses on the purported role HHV-6 plays in AD pathogenesis. First, early studies demonstrating evidence of HHV-6 cantonment in either post-mortem AD brain specimens or in peripheral blood samples of living AD patients are reviewed. Next, selected examples of possible mechanisms whereby viral infection can directly or indirectly contribute to AD pathogenesis are presented, such as autophagy dysregulation, the interaction between miR155 and HHV-6, and amyloid-beta as an antimicrobial peptide. Finally, closely related topics such as HHV-6 penetration in the CNS, HHV-6 involvement in neuroinflammation, and a brief discussion on HHV-6 epigenetics are examined.

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Section: Related Mechanisms and Future Research Directionsmentioning

confidence: 99%

The Role of Human Herpesvirus 6 Infection in Alzheimer’s Disease Pathogenicity—A Theoretical Mosaic

Romanescu

Schreiner

Mukovozov

2022

JCM

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“…Furthermore, SOCS1 induces differentiation from the M1 to M2 state and increased SOCS1 in the M2 phenotype, which plays an important role in sustaining the anti-inflammatory function [67]. Moreover, miR-155 can target M2-associated genes, and inhibition of miR-155 promotes the expression of M2 markers [68], such as Arg1, Ym1, and Fizz1. The above evidence suggests that the regulation of miR-124 and miR-155 in EAE has an important effect on the polarization of microglia, and the polarization of M1/M2 may also be accompanied by the changes of miR-124 and miR-155.…”

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confidence: 99%

Bu Shen Yi Sui Capsule Alleviates Neuroinflammation and Demyelination by Promoting Microglia toward M2 Polarization, Which Correlates with Changes in miR‐124 and miR‐155 in Experimental Autoimmune Encephalomyelitis

Zha

Gao

et al. 2021

Oxidative Medicine and Cellular Longevity

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Background. Bu Shen Yi Sui capsule (BSYS) is a traditional Chinese medicine prescription that has shown antineuroinflammatory and neuroprotective effects in treating multiple sclerosis (MS) and its animal model of experimental autoimmune encephalomyelitis (EAE). Microglia play an important role in neuroinflammation. The M1 phenotype of microglia is involved in the proinflammatory process of the disease, while the M2 phenotype plays an anti-inflammatory role. Promoting the polarization of microglia to M2 in MS/EAE is a promising therapeutic strategy. This study is aimed at exploring the effects of BSYS on microglial polarization in mice with EAE. Methods. The EAE model was established by the intraperitoneal injection of pertussis toxin and subcutaneous injection of myelin oligodendrocyte glycoprotein (MOG)35-55 in C57BL/6J mice. The mice were treated with BSYS (3.02 g/kg), FTY720 (0.3 mg/kg), or distilled water by intragastric administration. H&E and LFB staining, transmission electron microscopy, qRT-PCR, immunofluorescence, ELISA, fluorescence in situ hybridization, and western blotting were used to detect the histological changes in myelin, microglial M1/M2 polarization markers, and the expression of key genes involved in EAE. Results and Conclusions. BSYS treatment of EAE mice increased the body weight, decreased the clinical score, and reduced demyelination induced by inflammatory infiltration. BSYS also inhibited the mRNA expression of M1 microglial markers while increasing the mRNA level of M2 markers. Additionally, BSYS led to a marked decrease in the ratio of M1 microglia (iNOS+/Iba1+) and an obvious increase in the number of M2 microglia (Arg1+/Iba1+). In the EAE mouse model, miR-124 expression was decreased, and miR-155 expression was increased, while BSYS treatment significantly reversed this effect and modulated the levels of C/EBP α, PU.1, and SOCS1 (target genes of miR-124 and miR-155). Therefore, the neuroprotective effect of BSYS against MS/EAE was related to promoting microglia toward M2 polarization, which may be correlated with changes in miR-124 and miR-155 in vivo.

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“…In the present study, we found that DMY induced a switch from M1 to M2 phenotype polarization in microglia cells, which attenuates neuropathic pain. As neuropathic pain is mainly caused by M1 phenotype polarization, we constructed M1 phenotype polarization cells using LPS, as it is the common stimulator of M1 phenotype polarization (45,46). We further investigated the effects of DMY on M1/M2 phenotype polarization in the presence of LPS treatment, and found that the polarization of cells was increased with an increase in the DMY concentration in BV-2 cells.…”

Section: Discussionmentioning

confidence: 99%

Dihydromyricetin attenuates neuropathic pain via enhancing the transition from M1 to M2 phenotype polarization by potentially elevating ALDH2 activity in vitro and vivo

Zhang¹,

Yang²,

Li³

et al. 2020

Ann Transl Med

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Background: Treatment for neuropathic pain as a refractory disease remains unsatisfactory and represents a significant clinical challenge. A highly effective drug is thus urgently needed for neuropathic pain treatment. Dihydromyricetin (DMY) is a flavonoid with a wide range of biological activities. The purpose of this research is to explore the effects of DMY on neuropathic pain and the underlying mechanism of its effect.Methods: The effect of DMY was investigated in BV-2 cells and lipopolysaccharide (LPS)-induced BV-2 cells. A neuropathic pain model was established via spared nerve injury (SNI) surgery in mice, and the protein expression level was detected via Western blot assay. The percent of M1 and M2 phenotype polarization cells were detected via flow cytometry assay. Immunochemical staining assay was also performed to measure the marker levels of the M1 and M2 phenotype polarization cells and aldehyde dehydrogenase 2 (ALDH2) level, and mechanical pain sensitivity was evaluated via measurement of the mechanical withdrawal threshold.Results: We found that DMY promoted the transition from M1 to M2 polarization and upregulated the ALDH2 level in vitro and vitro. ALDA-1, an ALDH2 agonist, promoted the switching from M1 to M2 polarization in vivo and vitro. DMY alleviated pain hypersensitivity induced by SNI via enhancing M2 phenotype polarization by elevating ALDH2 activity in mice. After DMY-or ALDA-1-microglia were injected into SNI-induced pain hypersensitive mice, the mechanical withdrawal threshold was increased significantly when compared with the SNI group.Conclusions: Our data demonstrated that DMY alleviated neuropathic pain via enhancing the polarization transition from the M1 to M2 phenotype by potentially elevating ALDH2 activity in vitro and vivo. DMY-or ALDA-1-microglia may have alleviative effects on neuropathic pain. The findings herein provide a promising avenue for neuropathic pain treatment, suggesting a new target, ALDH2, in the treatment of neuropathic pain.

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Suppression of miR-155 attenuates neuropathic pain by inducing an M1 to M2 switch in microglia

Cited by 19 publications

References 50 publications

The Role of Human Herpesvirus 6 Infection in Alzheimer’s Disease Pathogenicity—A Theoretical Mosaic

The Role of Human Herpesvirus 6 Infection in Alzheimer’s Disease Pathogenicity—A Theoretical Mosaic

Bu Shen Yi Sui Capsule Alleviates Neuroinflammation and Demyelination by Promoting Microglia toward M2 Polarization, Which Correlates with Changes in miR‐124 and miR‐155 in Experimental Autoimmune Encephalomyelitis

Dihydromyricetin attenuates neuropathic pain via enhancing the transition from M1 to M2 phenotype polarization by potentially elevating ALDH2 activity in vitro and vivo

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