title: Neurotoxin quinolinic acid is selectively elevated in spinal cords of rats with experimental allergic encephalomyelitis.
abstract: Experimental allergic encephalomyelitis (EAE) is an autoimmune, animal model of multiple sclerosis (MS) in which demyelination and paralysis are evident. Quinolinic acid (QUIN) is a neurotoxin and endogenous N-methyl-D-aspartate receptor agonist formed from tryptophan. The role of neurotoxins in general and QUIN in particular in EAE or MS is unknown. Lewis rats inoculated with myelin basic protein developed signs of EAE by day 12, were killed, and their tissues assayed for QUIN by gas chromatography with mass spectrometry. QUIN levels were significantly elevated in the more caudal regions of the spinal cords of animals with EAE. Brain, serum, and liver levels of QUIN were not altered. In a similar manner, QUIN in mylin basic protein-injected, asymptomatic animals was not different from control animals. The time course for QUIN was similar to the neurological signs of the disorder; however, the initial elevation in QUIN occurred before the appearance of behavioral signs. Last, treatment with the glucocorticoid dexamethasone prevented both the signs of EAE and the elevation in spinal cord QUIN. It is not known whether QUIN contributes to the paralysis in EAE. However, if QUIN is pathogenic in EAE this finding could have therapeutic implications for MS.
authors.affiliation: Wellcome Research Laboratories, Research Triangle Park, North Carolina 27709.
authors.forename: E M
authors.initials: EM
authors.lastname: Flanagan
authors.forename: J B
authors.initials: JB
authors.lastname: Erickson
authors.forename: O H
authors.initials: OH
authors.lastname: Viveros
authors.forename: S Y
authors.initials: SY
authors.lastname: Chang
authors.forename: J F
authors.initials: JF
authors.lastname: Reinhard
mesh_terms: D000818:Animals; D003907:Dexamethasone / Q000494:pharmacology; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000378:metabolism* / Q000503:physiopathology; D008297:Male; D017378:Quinolinic Acid / Q000378:metabolism*; D051381:Rats; D011917:Rats, Inbred Lew; D013116:Spinal Cord / Q000378:metabolism*; D013997:Time Factors
chemical_list: D003907:Dexamethasone; D017378:Quinolinic Acid