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 language | English (US) |
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Pages (from-to) | 118-126 |
Number of pages | 9 |
Journal | Neurodegenerative Diseases |
Volume | 6 |
Issue number | 3 |
DOIs | |
State | Published - May 2009 |
Keywords
- Amyotrophic lateral sclerosis
- Immunoblotting
- Immunohistochemistry
- Inflammation
- Microglia
- Neuroinflammation
- Signal transducer and activator of transcription
ASJC Scopus subject areas
- Neurology
- Clinical Neurology