GLUTAMATE METABOLISM IS DOWN-REGULATED IN ASTROCYTES DURING EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS

Experimental allergic encephalomyelitis (EAE) was induced in SJL/J mic e 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 com plete paralysis of hind- and fore-limbs and tail (grade 4 EAE), thus e stablishing that reactive gliosis occurred under these experimental co nditions. Within the same samples and using similar techniques, we fou nd that glutamine synthetase (GS) and glutamate dehydrogenase (GDH) ex pression were dramatically reduced. These two astrocytic enzymes are r esponsible 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. (C) 1997 Wiley- Liss, Inc.