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Updated: Aug 20, 2026
Comprehensive Autopsy Program for Individuals with Multiple Sclerosis
Published on: July 19, 2019
Expression patterns of Group III metabotropic glutamate receptors mGluR4 and mGluR8 in multiple sclerosis lesions
J J G Geurts1, G Wolswijk, L Bö
1MS Research Center, VU Medical Center, Amsterdam, The Netherlands.
Abstract:
Recent evidence supports a role for metabotropic glutamate receptors (mGluRs) in neuroinflammatory diseases. In the present study, we have investigated whether the group III mGluR subtypes mGluR4 and mGluR8 are expressed in MS lesions at various stages of evolution. In control patient tissue and in normal-appearing MS white matter (NAWM), no microglial or astrocyte staining was detected. In contrast, in active lesions, mGluR8 immunoreactivity (IR) was detected in cells of the microglia/macrophage lineage. Fewer macrophage-like cells were positive for mGluR8 in chronic active and inactive lesions. No mGluR4 IR was detected in cells of the microglia/macrophage lineage in the MS lesions studied. In chronic active lesions, however, a population of reactive astrocytes localized in the rim of the lesions expressed both mGluR4 and mGluR8. Our results suggest a role for these receptor subtypes in the inflammatory response in MS that involves both astrocytes and cells of the microglia/macrophage lineage.
Insights
Metabotropic glutamate receptors (mGluRs) like mGluR8 are found in microglia/macrophages in active multiple sclerosis (MS) lesions. Reactive astrocytes in chronic active MS lesions also express mGluR4 and mGluR8, suggesting a role in neuroinflammation.
Area of Science:
- Neuroscience
- Immunology
- Pathology
Background:
- Metabotropic glutamate receptors (mGluRs) are implicated in neuroinflammatory diseases.
- The specific roles of group III mGluR subtypes, mGluR4 and mGluR8, in multiple sclerosis (MS) pathogenesis are not fully understood.
Purpose of the Study:
- To investigate the expression patterns of mGluR4 and mGluR8 in MS lesions at different stages of disease progression.
- To determine the cellular localization of these receptors within the lesions, focusing on microglia/macrophages and astrocytes.
Main Methods:
- Immunohistochemical analysis of MS patient tissue samples.
- Detection of mGluR4 and mGluR8 immunoreactivity (IR) in active, chronic active, and inactive MS lesions.
- Comparison of receptor expression in lesions versus normal-appearing white matter (NAWM) and control tissue.
Main Results:
- mGluR8 immunoreactivity was observed in microglia/macrophages within active MS lesions.
- The presence of mGluR8-positive microglia/macrophages decreased in chronic active and inactive lesions.
- No mGluR4 immunoreactivity was detected in microglia/macrophages in any MS lesion type.
- Both mGluR4 and mGluR8 were expressed by reactive astrocytes in the rim of chronic active MS lesions.
Conclusions:
- Group III mGluR subtypes, particularly mGluR8, are involved in the inflammatory response in MS.
- These receptors are expressed by both microglia/macrophages and reactive astrocytes in different stages of MS lesions.
- The findings suggest a potential therapeutic target for modulating neuroinflammation in MS.
