This is a historical research abstract about an experimental mouse model, not evidence of an established treatment for people with MS. Original author affiliation numbers, correspondence details and citation markers are preserved; the corresponding reference list was not included in this captured entry. Current scientific review and republication permission remain unverified.
Glutamate excitotoxicity in a model of multiple sclerosis
David Pitt2, 5, Peter Werner1, 3, 5 & Cedric S. Raine1, 2, 4
1. Department of Neurology, F-121N, Albert Einstein College of Medicine, 1300 Morris Park Ave., Bronx, New York, 10461, USA
2. Department of Pathology, F-121N, Albert Einstein College of Medicine, 1300 Morris Park Ave., Bronx, New York, 10461, USA
3. Dept. of Neurology, Beth Israel Medical Center, 10 Union Square East, New York, New York 10003, USA
4. Department of Neuroscience, F-121N, Albert Einstein College of Medicine, 1300 Morris Park Ave., Bronx , New York, 10461, USA
5. D.P and P.W. contributed equally to this study.
Correspondence should be addressed to P Werner. e-mail: pwerner@aecom.yu.edu.
Glutamate excitotoxicity mediated by the AMPA/kainate type of glutamate receptors damages not only neurons but also the myelin-producing cell of the central nervous system, the oligodendrocyte1. In multiple sclerosis, myelin, oligodendrocytes and some axons are lost as a result of an inflammatory attack on the central nervous system2. Because glutamate is released in large quantities by activated immune cells3, we expected that during inflammation in MS, glutamate excitotoxicity might contribute to the lesion. We addressed this by using the AMPA/kainate antagonist NBQX to treat mice sensitized for experimental autoimmune encephalomyelitis, a demyelinating model that mimics many of the clinical and pathologic features of multiple sclerosis. Treatment resulted in substantial amelioration of disease, increased oligodendrocyte survival and reduced dephosphorylation of neurofilament H, an indicator of axonal damage4. Despite the clinical differences, treatment with NBQX had no effect on lesion size and did not reduce the degree of central nervous system inflammation. In addition, NBQX did not alter the proliferative activity of antigen-primed T cells in vitro, further indicating a lack of effect on the immune system. Thus, glutamate excitotoxicity seems to be an important mechanism in autoimmune demyelination, and its prevention with AMPA/kainate antagonists may prove to be an effective therapy for multiple sclerosis.
Source details
Author: David Pitt2, 5, Peter Werner1, 3, 5 & Cedric S. Raine1, 2, 4
Archive capture: . This is not a medical review date.