Reactive astrocytes express the potassium channel Kir4.1 in active multiple sclerosis lesions
Version of Record online: 5 APR 2013
© 2013 Japanese Society for Neuroimmunology
Clinical and Experimental Neuroimmunology
Volume 4, Issue 1, pages 19–28, June 2013
How to Cite
(Clin. Exp. Neuroimmunol. doi: 10.1111/cen3.12011, March 2013)
- Issue online: 10 JUN 2013
- Version of Record online: 5 APR 2013
- Manuscript Accepted: 19 FEB 2013
- Manuscript Revised: 18 FEB 2013
- Manuscript Received: 14 JAN 2013
- Research on Intractable Diseases
- Ministry of Health, Labour and Welfare
- High-Tech Research Center Project. Grant Number: S0801043
- Genome Research Center Project
- Grant-in-Aid. Grant Number: C22500322
- Ministry of Education, Culture, Sports, Science and Technology
- Alzheimer's disease;
- multiple sclerosis;
- reactive astrocytes
Kir4.1, an inwardly rectifying potassium channel expressed on perivascular and perisynaptic end-feet of astrocytes, plays a pivotal role in the spatial buffering of the potassium in the brain. A recent study showed that autoantibodies directed to Kir4.1 are detectable in the serum derived from approximately half of the patients with multiple sclerosis (MS) and clinically isolated syndrome, although their pathogenic roles should be elucidated.
We studied Kir4.1 expression in MS and control brains by immunohistochemistry.
We found that reactive astrocytes expressed an intense immunoreactivity for Kir4.1 in active demyelinating lesions of MS, active lesion edges of neuromyelitis optica, ischemic lesion edges of cerebral infarction and neurodegenerative lesions of Alzheimer's disease. Reactive astrocytes accumulated in active MS lesions coexpressed Kir4.1 and AQP4. A subset of amyloid plaques in Alzheimer's disease brains also expressed Kir4.1. In contrast, infiltrating macrophages, activated microglia and surviving oligodendrocytes in active MS lesions did not express Kir4.1. Furthermore, cultured human astrocytes expressed Kir4.1, and the expression levels were not altered by exposure to tumor necrosis factor-α or interleukin-1β, but were elevated by transforming growth factor-β1.
These results show that reactive astrocytes abundantly express Kir4.1, and Kir4.1 immunoreactivity is not lost in active demyelinating lesions of MS.