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Up-regulated p75NTR neurotrophin receptor on glial cells in MS plaques
1Neurology Service, Department of Veterans Affairs, New Jersey Health Care System, East Orange VA Medical Center, 07018, USA.
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.
Insights
The neurotrophin receptor p75NTR is elevated in glial cells within multiple sclerosis (MS) plaques. Its precise role in MS glial cell death and survival requires further investigation.
Area of Science:
- Neuroscience
- Immunology
- Pathology
Background:
- Multiple sclerosis (MS) pathogenesis involves inflammatory and resident glial cells, including oligodendrocytes undergoing cell death.
- Increased expression of Fas receptor and ligand death pathway signaling molecules is observed on glial cells in MS plaques.
- p75NTR can induce apoptotic death in oligodendrocytes when exposed to nerve growth factor (NGF) in vitro.
Purpose of the Study:
- To investigate the expression of the neurotrophin receptor p75NTR on glial cells within MS plaques.
- To determine the correlation between p75NTR expression and glial cell death in MS.
Main Methods:
- Immunohistochemistry and in situ reverse-transcription PCR were used to detect p75NTR expression.
- TUNEL staining was employed to identify fragmented DNA, indicating cell death.
Main Results:
- Up-regulated p75NTR messenger RNA and protein were detected in oligodendrocytes and microglia/macrophages within MS plaques.
- p75NTR expression was absent in control white matter samples.
- Only a subset of p75NTR-expressing oligodendrocytes showed evidence of cell death via TUNEL staining.
Conclusions:
- Glial cell expression of the p75NTR receptor is increased during the formation of MS plaques.
- The specific function of p75NTR in glial cell death and/or survival within the context of MS remains to be determined.
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