Glutamate metabolism is down-regulated in astrocytes during experimental allergic encephalomyelitis.
Experimental allergic encephalomyelitis (EAE) was induced in SJL/J mice by adoptive transfer of MBP-reactive T cells in order to investigate the role of astrocytes in pathology. GFAP protein and mRNA expression (analyzed using semiquantitative Western blot and RT-PCR techniques) were upregulated in the spinal cord of mice, which had developed a complete paralysis of hind- and fore-limbs and tail (grade 4 EAE), thus establishing that reactive gliosis occurred under these experimental conditions. Within the same samples and using similar techniques, we found that glutamine synthetase (GS) and glutamate dehydrogenase (GDH) expression were dramatically reduced. These two astrocytic enzymes are responsible for degradation of glutamate, the most abundant excitatory neurotransmitter in the brain. Since elevated levels of glutamate may be neurotoxic, we propose that the decreased capacity of astrocytes to metabolize glutamate may contribute to EAE pathology.
Hardin-Pouzet
H
H
Neuroimmunology Unit, Montreal Neurological Institute, Québec, Canada.
Krakowski
M
M
Bourbonnière
L
L
Didier-Bazes
M
M
Tran
E
E
Owens
T
T
D019264:Adoptive Transfer; D000818:Animals; D001253:Astrocytes / Q000378:metabolism*; D001921:Brain / Q000378:metabolism; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000378:metabolism* / Q000503:physiopathology; D005260:Female; D005904:Glial Fibrillary Acidic Protein / Q000096:biosynthesis; D005969:Glutamate Dehydrogenase / Q000096:biosynthesis; D005974:Glutamate-Ammonia Ligase / Q000096:biosynthesis; D018698:Glutamic Acid / Q000378:metabolism*; D051379:Mice; D008815:Mice, Inbred Strains; D004676:Myelin Basic Protein / Q000276:immunology; D010243:Paralysis; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000096:biosynthesis; D013116:Spinal Cord / Q000378:metabolism*; D013601:T-Lymphocytes / Q000276:immunology; D014158:Transcription, Genetic
D005904:Glial Fibrillary Acidic Protein; D004676:Myelin Basic Protein; D012333:RNA, Messenger; D018698:Glutamic Acid; D005969:Glutamate Dehydrogenase; D005974:Glutamate-Ammonia Ligase