Alterations in glutamate transport and group I metabotropic glutamate receptors in the rat brain during acute phase of experimental autoimmune encephalomyelitis.
Experimental autoimmune encephalomyelitis (EAE) is an animal model that mimics many aspects of multiple sclerosis (MS). In MS the immune system attacks the white matter of the brain and spinal cord, leading to disability and paralysis. Neurons, oligodendrocytes and myelin are lost due to the release of cytotoxic cytokines, autoantibodies and toxic amounts of the excitatory neurotransmitter glutamate. This study was designed to determine the changes in: a) glutamate transport in nerve endings and astroglial fraction, b) level of excitatory amino acid transporters (EAATs) and c) level of group I metabotropic glutamate receptors (mGluR G I) protein in the acute phase of EAE (12 d.p.i. - day post immunization), in the peak of neurological deficits. We have found that glutamate uptake in synaptosomes and GPV fraction increases by about 30% and 15%, respectively, compared to controls. We also observed an increase in KCl-dependent glutamate release from synaptosomes and GPV fraction obtained from EAE rats by about 20%. Western blots analysis of protein expression shows elevation of group I metabotropic glutamate receptors (mGluR G I) and excitatory amino acid transporters (EAATs) in EAE rats during the acute phase of the disease (12 d.p.i), when the level of proinflammatory cytokines (IL-1beta, IL-6, TNF-alpha) rises. The results suggest that during the inflammatory conditions in the acute phase of EAE, disturbances in glutamate transport take place that may lead to the excitotoxicity.
Sulkowski
Grzegorz
G
Laboratory of Pathoneurochemistry, Department of Neurochemistry, Mossakowski Medical Research Centre, Polish Academy of Sciences, 5 Pawińskiego Str., 02-106 Warsaw, Poland. sulgrzeg@cmdik.pan.pl
Dabrowska-Bouta
Beata
B
Kwiatkowska-Patzer
Barbara
B
Struzyńska
Lidia
L
D000818:Animals; D001253:Astrocytes / Q000378:metabolism; D001692:Biological Transport / Q000502:physiology; D015153:Blotting, Western; D001921:Brain / Q000378:metabolism*; D016207:Cytokines / Q000378:metabolism; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000378:metabolism*; D005260:Female; D050491:Glutamate Plasma Membrane Transport Proteins / Q000378:metabolism*; D018698:Glutamic Acid / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism; D051381:Rats; D018094:Receptors, Metabotropic Glutamate / Q000378:metabolism*; D013574:Synaptosomes / Q000378:metabolism; D013997:Time Factors
D016207:Cytokines; D050491:Glutamate Plasma Membrane Transport Proteins; D018094:Receptors, Metabotropic Glutamate; D018698:Glutamic Acid