title: N-Methyl-D-aspartate (NMDA) receptor involvement in central nervous system prostaglandin production during the relapse phase of chronic relapsing experimental autoimmune encephalomyelitis (CR EAE).
abstract: Our previous studies have established that major changes in central nervous system (CNS) prostaglandin (PG) levels occur during the relapse phase of chronic relapsing experimental autoimmune encephalomyelitis (CR EAE), an animal model of the human demyelinating disease multiple sclerosis. PG production is controlled through a series of enzymic pathways that, in EAE, are influenced by neuroantigen-driven autoimmune events. In non-immune-based models of CNS disease, endogenous glucocorticoids have been proposed as instigators of PG synthesis via activation of the N-methyl-D-aspartate (NMDA) receptor. Glucocorticoids have an important regulatory role in the pathogenesis EAE and the NMDA receptor is intimately involved in many of the characteristic neuroinflammatory processes that govern the disease. Therefore, the alterations in prostanoid concentrations during the relapse stage of CR EAE may ultimately be governed by glucocorticoid-induced NMDA receptor activation. The current investigation has examined the proposed glucocorticoid-NMDA receptor link by determining the effects of the receptor antagonist, (+) MK-801, on CNS PGE 2 and PGD 2 levels in Biozzi mice with relapse symptoms of CR EAE. Prostanoid concentrations in the cerebral cortex were not altered by drug administration, and in cerebellar tissues, a vehicle effect negated any drug-induced changes. However, the level of PGD 2 in spinal cords from (+) MK-801-dosed mice was significantly lower, compared to controls, but PGE 2 concentrations remained unchanged. The results suggest that glucocorticoid-NMDA receptor-linked events are not primarily responsible for PG generation in the brain but may influence prostanoid production in discrete areas of the CNS.
authors: Neuroimmunology Unit, Centre for Neuroscience and Trauma, Blizard Institute of Cell and Molecular Science, St. Bartholomew's and The London School of Medicine and Dentistry, 4, Newark Street, London, E12 AT, UK.
authors: Christopher
authors: C
authors: Bolton
authors: Elizabeth G
authors: EG
authors: Wood
authors: Samir S
authors: SS
authors: Ayoub
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use; D002490:Central Nervous System / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D015232:Dinoprostone / Q000378:metabolism*; D016291:Dizocilpine Maleate / Q000627:therapeutic use; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000188:drug therapy / Q000276:immunology / Q000378:metabolism*; D018691:Excitatory Amino Acid Antagonists / Q000627:therapeutic use; D005938:Glucocorticoids / Q000378:metabolism; D008297:Male; D051379:Mice; D038602:Mice, Biozzi; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000188:drug therapy / Q000276:immunology / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D018733:Nicotinic Antagonists / Q000627:therapeutic use; D015230:Prostaglandin D2 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011897:Random Allocation; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors / Q000378:metabolism*; D012008:Recurrence; D013116:Spinal Cord / Q000187:drug effects / Q000276:immunology / Q000378:metabolism
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D018691:Excitatory Amino Acid Antagonists; D005938:Glucocorticoids; D009419:Nerve Tissue Proteins; D018733:Nicotinic Antagonists; D016194:Receptors, N-Methyl-D-Aspartate; D016291:Dizocilpine Maleate; D015232:Dinoprostone; D015230:Prostaglandin D2