Appearance of phagocytic microglia adjacent to motoneurons in spinal cord tissue from a presymptomatic transgenic rat model of amyotrophic lateral sclerosis

Tomomi Sanagi, Shigeki Yuasa, Yasuko Nakamura, Eri Suzuki, Masashi Aoki, Hitoshi Warita, Yasuto Itoyama, Shigeo Uchino, Shinichi Kohsaka, Keiko Ohsawa

Research output: Contribution to journalArticlepeer-review

41 Citations (Scopus)

Abstract

Microglial activation occurs early during the pathogenesis of amyotrophic lateral sclerosis (ALS). Recent evidence indicates that the expression of mutant Cu2+/Zn2+ superoxide dismutase 1 (SOD1) in microglia contributes to the late disease progression of ALS. However, the mechanism by which microglia influence the neurodegenerative process and disease progression in ALS remains unclear. In this study, we revealed that activated microglia aggregated in the lumbar spinal cord of presymptomatic mutant SOD1 H46R transgenic rats, an animal model of familial ALS. The aggregated microglia expressed a marker of proliferating cell, Ki67, and phagocytic marker proteins ED1 and major histocompatibility complex (MHC) class II. The motoneurons near the microglial aggregates showed weak choline acetyltransferase (ChAT) immunoreactivity and contained reduced granular endoplasmic reticulum and altered nucleus electron microscopically. Furthermore, immunopositive signals for tumor necrosis factor-α (TNFα) and monocyte chemoattractant protein-1 (MCP-1) were localized in the aggregated microglia. These results suggest that the activated and aggregated microglia represent phagocytic features in response to early changes in motoneurons and possibly play an important role in ALS disease progression during the presymptomatic stage.

Original languageEnglish
Pages (from-to)2736-2746
Number of pages11
JournalJournal of Neuroscience Research
Volume88
Issue number12
DOIs
Publication statusPublished - 2010 Sep 1

Keywords

  • Electron microscopy
  • Immunohistochemistry
  • Microglia
  • Mutant SOD1
  • Phagocytosis

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience

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