Chemogenetic manipulation of microglia inhibits neuroinflammation and neuropathic pain in mice

Copyright © 2020 Elsevier Inc. All rights reserved..

Microglia play an important role in the central sensitization and chronic pain. However, a direct connection between microglial function and pain development in vivo remains incompletely understood. To address this issue, we applied chemogenetic approach by using CX3CR1creER/+:R26LSL-hM4Di/+ transgenic mice to enable expression of inhibitory Designer Receptors Exclusively Activated by Designer Drugs (Gi DREADD) in microglia. We found that microglial Gi DREADD activation inhibited spinal nerve transection (SNT)-induced microglial reactivity as well as chronic pain in both male and female mice. Gi DREADD activation downregulated the transcription factor interferon regulatory factor 8 (IRF8) and its downstream target pro-inflammatory cytokine interleukin 1 beta (IL-1β). Using in vivo spinal cord recording, we found that activation of microglial Gi DREADD attenuated synaptic transmission following SNT. Our results demonstrate that microglial Gi DREADD reduces neuroinflammation, synaptic function and neuropathic pain after SNT. Thus, chemogenetic approaches provide a potential opportunity for interrogating microglial function and neuropathic pain treatment.

Medienart:

E-Artikel

Erscheinungsjahr:

2021

Erschienen:

2021

Enthalten in:

Zur Gesamtaufnahme - volume:92

Enthalten in:

Brain, behavior, and immunity - 92(2021) vom: 15. Feb., Seite 78-89

Sprache:

Englisch

Beteiligte Personen:

Yi, Min-Hee [VerfasserIn]
Liu, Yong U [VerfasserIn]
Liu, Kevin [VerfasserIn]
Chen, Tingjun [VerfasserIn]
Bosco, Dale B [VerfasserIn]
Zheng, Jiaying [VerfasserIn]
Xie, Manling [VerfasserIn]
Zhou, Lijun [VerfasserIn]
Qu, Wenchun [VerfasserIn]
Wu, Long-Jun [VerfasserIn]

Links:

Volltext

Themen:

CX3CR1
Chemogenetics
Gi DREADD
IL-1β
IRF8
Journal Article
Microglia
Neuropathic pain
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
SNT

Anmerkungen:

Date Completed 27.05.2021

Date Revised 02.02.2022

published: Print-Electronic

Citation Status MEDLINE

doi:

10.1016/j.bbi.2020.11.030

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM317885073