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

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.

• Authors: Hidetoshi Tozaki-Saitoh, Junya Masuda, Ryu Kawada, Chinami Kojima, Sosuke Yoneda, Takahiro Masuda, Kazuhide Inoue, Makoto Tsuda
• Journal: Glia (Glia) Vol. 67 Issue 4 Pg. 729-740 (04 2019) ISSN: 1098-1136 [Electronic] United States
• PMID: 30485546 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2018 Wiley Periodicals, Inc.

Chemical References

• Aif1 protein, mouse
• CD11b Antigen
• Calcium-Binding Proteins
• Glial Fibrillary Acidic Protein
• MafB Transcription Factor
• Mafb protein, mouse
• Microfilament Proteins
• RNA, Messenger
• RNA, Small Interfering
• Green Fluorescent Proteins
• Phosphopyruvate Hydratase

Topics

• Animals
• CD11b Antigen (metabolism)
• Calcium-Binding Proteins (metabolism)
• Cells, Cultured
• Disease Models, Animal
• Embryo, Mammalian
• Gene Expression Regulation (genetics)
• Glial Fibrillary Acidic Protein (metabolism)
• Green Fluorescent Proteins (genetics, metabolism)
• Hyperalgesia (genetics, physiopathology)
• MafB Transcription Factor (genetics, metabolism)
• Male
• Mice
• Mice, Inbred C57BL
• Mice, Transgenic
• Microfilament Proteins (metabolism)
• Microglia (metabolism, transplantation)
• Neuralgia (drug therapy, pathology)
• Pain Threshold (physiology)
• Phosphopyruvate Hydratase (genetics, metabolism)
• RNA, Messenger (metabolism)
• RNA, Small Interfering (therapeutic use)
• Spinal Cord (pathology)