Brain Advance Access originally published online on June 4, 2003
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Brain, Vol. 126, No. 8, 1755-1766,
August 2003
© 2003 Guarantors of Brain
doi: 10.1093/brain/awg179
Altered expression patterns of group I and II metabotropic glutamate receptors in multiple sclerosis
1 Department of Radiology, 2 Department of Neurology, MR Center for MS Research, 3 Department of Pathology, Division of Neuropathology, Vrije Universiteit Medical Center, 4 Netherlands Institute for Brain Research and 5 Department of (Neuro) Pathology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands
Correspondence to: Dr E. Aronica, Department of (Neuro) Pathology, Academic Medical Center, Meibergdreef 9, 91105, AZ Amsterdam, The Netherlands E-mail: e.aronica{at}amc.uva.nl
Recent evidence supports a role for glutamate receptors in the pathophysiology of multiple sclerosis. In the present study, we have focused specifically on the expression of metabotropic glutamate receptors (mGluRs) in multiple sclerosis brain tissue. The expression of group I (mGluR1
and mGluR5) and group II (mGluR2/3) mGluRs was studied using immunohistochemistry in tissue from 12 multiple sclerosis cases and seven non-neurological controls. The expression patterns of both group I and II mGluRs in multiple sclerosis tissue differed significantly from those in control tissue. Strong mGluR1 immunoreactivity was observed in axons of the subcortical white matter, particularly in the centre of actively demyelinating lesions and in the borders of chronic active lesions. mGluR1 axonal immunopositivity was also found in normal appearing multiple sclerosis white matter, but axons in control white matter were generally negative. mGluR1 axonal labelling was associated with the presence of non-phosphorylated neurofilaments and ß-amyloid precursor protein, which are sensitive markers for axonal injury and disturbed axonal transport. Changes in mGluR immunoreactivity were also observed in glia. A diffuse increase in the expression of mGluR5 and mGluR2/3 was detected in reactive astrocytes in multiple sclerosis lesions. However, only a subpopulation of reactive astroglial cells expressed mGluR1. In addition, labelling with antibodies to mGluR2/3 and, to a lesser extent labelling with antibodies to mGluR1, was detected in a population of cells of the microglial/macrophage lineage that displayed a macrophage-like morphology. Our data suggest that mGluRs, like ionotropic glutamate receptors, play a role in the complex processes that are associated with the progressive brain damage in multiple sclerosis, including both glial activation and pathological changes in axons.
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