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


CONCLUSIONS
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.
Department of Pathology, Tokyo Women's Medical University, Shinjuku-ku, Tokyo, Japan. shibatan@research.twmu.ac.jp
Noriyuki
N
Shibata
Akiyoshi
A
Kakita
Hitoshi
H
Takahashi
Yuetsu
Y
Ihara
Keigo
K
Nobukuni
Harutoshi
H
Fujimura
Saburo
S
Sakoda
Shoichi
S
Sasaki
Makoto
M
Iwata
Shunichi
S
Morikawa
Asao
A
Hirano
Makio
M
Kobayashi
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000690:Amyotrophic Lateral Sclerosis / Q000378:metabolism* / Q000473:pathology; D015153:Blotting, Western; D004789:Enzyme Activation / Q000502:physiology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D017628:Microglia / Q000378:metabolism; D008875:Middle Aged; D010766:Phosphorylation; D021381:Protein Transport / Q000502:physiology; D050796:STAT3 Transcription Factor / Q000378:metabolism*; D013116:Spinal Cord / Q000378:metabolism* / Q000473:pathology; D015854:Up-Regulation
D050796:STAT3 Transcription Factor