Open AccessGlutamate Receptor Expression in Multiple Sclerosis Lesions
Author(s) -
Newcombe Jia,
Uddin Alim,
Dove Rosamund,
Patel Bela,
Turski Lechoslaw,
Nishizawa Yukio,
Smith Terence
Publication year - 2008
Publication title -
brain pathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.986
H-Index - 132
eISSN - 1750-3639
pISSN - 1015-6305
DOI - 10.1111/j.1750-3639.2007.00101.x
Subject(s) - ampa receptor , glutamate receptor , metabotropic glutamate receptor 1 , metabotropic glutamate receptor 5 , kainate receptor , metabotropic glutamate receptor 6 , metabotropic glutamate receptor , metabotropic glutamate receptor 7 , metabotropic glutamate receptor 2 , ionotropic glutamate receptor , metabotropic glutamate receptor 8 , biology , astrocyte , excitotoxicity , nmda receptor , neuroscience , microbiology and biotechnology , receptor , biochemistry , central nervous system
Blockade of receptors for the excitatory neurotransmitter glutamate ameliorates neurological clinical signs in models of the CNS inflammatory demyelinating disease multiple sclerosis (MS). To investigate whether glutamate excitoxicity may play a role in MS pathogenesis, the cellular localization of glutamate and its receptors, transporters and enzymes was examined. Expression of glutamate receptor (GluR) 1, a Ca ++ ‐permeable ionotropic AMPA receptor subunit, was up‐regulated on oligodendrocytes in active MS lesion borders, but Ca ++ ‐impermeable AMPA GluR2 subunit levels were not increased. Reactive astrocytes in active plaques expressed AMPA GluR3 and metabotropic mGluR1, 2/3 and 5 receptors and the GLT‐1 transporter, and a subpopulation was immunostained with glutamate antibodies. Activated microglia and macrophages were immunopositive for GluR2, GluR4 and NMDA receptor subunit 1. Kainate receptor GluR5–7 immunostaining showed endothelial cells and dystrophic axons. Astrocyte and macrophage populations expressed glutamate metabolizing enzymes and unexpectedly the EAAC1 transporter, which may play a role in glutamate uptake in lesions. Thus, reactive astrocytes in MS white matter lesions are equipped for a protective role in sequestering and metabolizing extracellular glutamate. However, they may be unable to maintain glutamate at levels low enough to protect oligodendrocytes rendered vulnerable to excitotoxic damage because of GluR1 up‐regulation.