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A Kv1.3 channel-specific blocker alleviates neurological impairment through inhibiting T-cell activation in experimental autoimmune encephalomyelitis.
- Source :
-
CNS neuroscience & therapeutics [CNS Neurosci Ther] 2018 Oct; Vol. 24 (10), pp. 967-977. Date of Electronic Publication: 2018 Mar 25. - Publication Year :
- 2018
-
Abstract
- Aim: Multiple sclerosis (MS) is a neurological autoimmune disorder characterized by mistaken attacks of inflammatory cells against the central nervous system (CNS), resulting in demyelination and axonal damage. Kv1.3 channel blockers can inhibit T-cell activation and have been designed for MS therapy. However, little is known about the effects of Kv1.3 blockers on protecting myelin sheaths/axons in MS. This study aimed at investigating the neuroprotection efficacy of a selective Kv1.3 channel blocker ImKTx88 (ImK) in MS animal model.<br />Methods: Experimental autoimmune encephalomyelitis (EAE) rat model was established. The neuroprotective effect of ImK was assessed by immunohistochemistry and transmission electron microscopy (TEM). In addition, the antiinflammatory effect of ImK by suppressing T-cell activation was assessed by flow cytometry and ELISA in vitro.<br />Results: Our results demonstrated that ImK administration ameliorated EAE clinical severity. Moreover, ImK increased oligodendrocytes survival, preserved axons, and myelin integrity and reduced the infiltration of activated T cells into the CNS. This protective effect of the peptide may be related to its suppression of autoantigen-specific T-cell activation via calcium influx inhibition.<br />Conclusion: ImK prevents neurological damage by suppressing T-cell activation, suggesting the applicability of this peptide in MS therapy.<br /> (© 2018 John Wiley & Sons Ltd.)
- Subjects :
- Animals
Animals, Newborn
Cells, Cultured
Disease Models, Animal
Female
Kv1.3 Potassium Channel antagonists & inhibitors
Microscopy, Electron, Transmission
Mycobacterium tuberculosis pathogenicity
Myelin Basic Protein metabolism
Nerve Tissue Proteins metabolism
Neurons drug effects
Neurons metabolism
Rats
Rats, Sprague-Dawley
T-Lymphocytes drug effects
T-Lymphocytes ultrastructure
Encephalomyelitis, Autoimmune, Experimental complications
Kv1.3 Potassium Channel metabolism
Nervous System Diseases drug therapy
Nervous System Diseases etiology
Potassium Channel Blockers therapeutic use
T-Lymphocytes physiology
Subjects
Details
- Language :
- English
- ISSN :
- 1755-5949
- Volume :
- 24
- Issue :
- 10
- Database :
- MEDLINE
- Journal :
- CNS neuroscience & therapeutics
- Publication Type :
- Academic Journal
- Accession number :
- 29577640
- Full Text :
- https://doi.org/10.1111/cns.12848