Activation of signal transducer and activator of transcription-3 in the spinal cord of sporadic amyotrophic lateral sclerosis patients

Noriyuki Shibata, Akiyoshi Kakita, Hitoshi Takahashi, Yuetsu Ihara, Keigo Nobukuni, Harutoshi Fujimura, Saburo Sakoda, Shoichi Sasaki, Makoto Iwata, Shunichi Morikawa, Asao Hirano, Makio Kobayashi

Research output: Contribution to journalArticle

23 Scopus citations

Abstract

Background: Neuroinflammation has been implicated in the pathomechanism of amyotrophic lateral sclerosis (ALS). It is known that signal transducer and activator of transcription-3 (STAT3) is a proinflammatory transcription factor. However, it remains to be determined whether STAT3 is involved in ALS. Objective: To test the hypothesis that STAT3 may be upregulated, activated, or both in the spinal cord of ALS patients. Methods: We performed immunohistochemical, immunoblot and densitometric analyses of total STAT3 (t-STAT3) or phosphorylated active form of STAT3 (p-STAT3) in spinal cords obtained at autopsy from 10 sporadic ALS patients and 10 age-matched control subjects. Results: On sections, p-STAT3 immunoreactivity was localized in the nucleus as well as the cytoplasm of almost all activated microglia in the ALS cases, while it was detectable in a few resting microglia in the control cases. On blots, densitometric p-STAT3 levels in nuclear protein extracts significantly increased in the ALS group compared with the control group, although there was no significant difference in densitometric t-STAT3 levels in cytosolic protein extracts between the two groups. Additionally, there was no significant relationship between the nuclear p-STAT3 levels in the ALS cases and the clinical phenotypes, age at death, or disease duration. Conclusion: The present results suggest that persistent activation and nuclear translocation but not upregulation of STAT3 occurs in ALS spinal cord microglia, which may regulate inflammatory activity.

Original languageEnglish (US)
Pages (from-to)118-126
Number of pages9
JournalNeurodegenerative Diseases
Volume6
Issue number3
DOIs
Publication statusPublished - May 1 2009

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Keywords

  • Amyotrophic lateral sclerosis
  • Immunoblotting
  • Immunohistochemistry
  • Inflammation
  • Microglia
  • Neuroinflammation
  • Signal transducer and activator of transcription

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology

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