Transcription factor MafB contributes to the activation of spinal microglia underlying neuropathic pain development

Hidetoshi Saitoh, Junya Masuda, Ryu Kawada, Chinami Kojima, Sosuke Yoneda, Takahiro Masuda, Kazuhide Inoue, Tsuda Makoto

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Microglia, which are pathological effectors and amplifiers in the central nervous system, undergo various forms of activation. A well-studied microglial-induced pathological paradigm, spinal microglial activation following peripheral nerve injury (PNI), is a key event for the development of neuropathic pain but the transcription factors contributing to microglial activation are less understood. Herein, we demonstrate that MafB, a dominant transcriptional regulator of mature microglia, is involved in the pathology of a mouse model of neuropathic pain. PNI caused a rapid and marked increase of MafB expression selectively in spinal microglia but not in neurons. We also found that the microRNA mir-152 in the spinal cord which targets MafB expression decreased after PNI, and intrathecal administration of mir-152 mimic suppressed the development of neuropathic pain. Reduced MafB expression using heterozygous Mafb deficient mice and by intrathecal administration of siRNA alleviated the development of PNI-induced mechanical hypersensitivity. Furthermore, we found that intrathecal transfer of Mafb deficient microglia did not induce mechanical hypersensitivity and that conditional Mafb knockout mice did not develop neuropathic pain after PNI. We propose that MafB is a key mediator of the PNI-induced phenotypic alteration of spinal microglia and neuropathic pain development.

Original languageEnglish
Pages (from-to)729-740
Number of pages12
JournalGLIA
Volume67
Issue number4
DOIs
Publication statusPublished - Apr 1 2019

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MafB Transcription Factor
Peripheral Nerve Injuries
Microglia
Neuralgia
Hypersensitivity
MicroRNAs
Knockout Mice
Small Interfering RNA
Spinal Cord
Transcription Factors
Central Nervous System
Pathology
Neurons

All Science Journal Classification (ASJC) codes

  • Neurology
  • Cellular and Molecular Neuroscience

Cite this

Transcription factor MafB contributes to the activation of spinal microglia underlying neuropathic pain development. / Saitoh, Hidetoshi; Masuda, Junya; Kawada, Ryu; Kojima, Chinami; Yoneda, Sosuke; Masuda, Takahiro; Inoue, Kazuhide; Makoto, Tsuda.

In: GLIA, Vol. 67, No. 4, 01.04.2019, p. 729-740.

Research output: Contribution to journalArticle

Saitoh, Hidetoshi ; Masuda, Junya ; Kawada, Ryu ; Kojima, Chinami ; Yoneda, Sosuke ; Masuda, Takahiro ; Inoue, Kazuhide ; Makoto, Tsuda. / Transcription factor MafB contributes to the activation of spinal microglia underlying neuropathic pain development. In: GLIA. 2019 ; Vol. 67, No. 4. pp. 729-740.
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AU - Inoue, Kazuhide

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