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From the Neurology Service (Drs. Dowling, Raval, Husar, Cook, and Blumberg), Department of Veterans Affairs, New Jersey Health Care System, East Orange VA Medical Center, East Orange, NJ; Department of Neurosciences (Drs. Dowling, Ming, Husar, Cook, and Blumberg), UMD–New Jersey Medical School, Newark, NJ; and §Skirball Institute (Drs. Casaccia-Bonnefil and Chao), New York University Medical Center, New York, NY.
Address correspondence and reprint requests to Dr. Peter Dowling, Neurology Service, VA New Jersey Health Care System, 385 Tremont Avenue, East Orange, NJ 07018.
OBJECTIVE: To investigate the expression of the neurotrophin receptor p75NTR on glial cells within MS plaques. Background: In recent studies on the pathogenesis of MS white matter plaques, we found large populations of inflammatory and resident glial cells, including oligodendrocytes undergoing cell death, and identified increased expression of Fas receptor and ligand death pathway signaling molecules on the same glial cell types. In another study, the p75NTR was shown to induce apoptotic death of maturing oligodendrocytes when exposed to NGF in vitro. Methods: We used immunohistochemistry and in situ reverse-transcription PCR to detect p75NTR expression on inflammatory and resident glial cells in MS plaques and used TUNEL staining for fragmented DNA to detect cell death. Results: Up-regulated p75NTR messenger RNA and protein were demonstrated in both oligodendrocytes and microglia/macrophages in MS plaques but not in control white matter. However, only a fraction of p75NTR expressing oligodendrocytes was also stained by TUNEL. Conclusions: Glial cell expression of p75NTR receptor is up-regulated during MS plaque formation. The exact role of this receptor in glial cell death and/or survival in MS remains to be elucidated.
Key words: neurotrophin receptor p75NTR—glial cells—white matter plaques—MS.
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