The neurotoxin quinolinic acid is increased in spinal cords of mice with herpes simplex virus encephalitis.
Following retroperitoneal, intradermal inoculation of mice with HSV-1, signs of encephalomyelitis (hind-limb paralysis, flaccid tail and loss of bladder control) appeared 6-7 days later. Levels of quinolinic acid (QUIN; determined by gas chromatography with mass-spectrometry), rose approximately 40-fold in mice with encephalomyelitis, primarily in the spinal cord. Live virus could also be grown from homogenates of the affected spinal cords. Time-course studies, demonstrated that the increase in QUIN coincided with the appearance of encephalomyelitis. Large increases in indoleamine dioxygenase activity were observed in spinal cords from the affected mice, suggesting that the QUIN was synthesized within the spinal cord. It is, therefore, possible that QUIN may contribute to the pathology of HSV-1 encephalomyelitis.
Wellcome Research Laboratories, Research Triangle Park, North Carolina, USA.
J F
JF
Reinhard
E M
EM
Flanagan
D050561:3-Hydroxyanthranilate 3,4-Dioxygenase; D000818:Animals; D049308:Dioxygenases; D018792:Encephalitis, Viral / Q000378:metabolism* / Q000503:physiopathology; D008401:Gas Chromatography-Mass Spectrometry; D006561:Herpes Simplex / Q000378:metabolism* / Q000503:physiopathology; D018259:Herpesvirus 1, Human; D006867:Hydrolases / Q000378:metabolism; D050601:Kynurenine 3-Monooxygenase; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D006899:Mixed Function Oxygenases / Q000378:metabolism; D009498:Neurotoxins; D010105:Oxygenases / Q000378:metabolism; D012016:Reference Values; D013116:Spinal Cord / Q000378:metabolism*; D014366:Tryptophan Oxygenase / Q000378:metabolism
D009498:Neurotoxins; D006899:Mixed Function Oxygenases; D010105:Oxygenases; D049308:Dioxygenases; D014366:Tryptophan Oxygenase; D050561:3-Hydroxyanthranilate 3,4-Dioxygenase; D050601:Kynurenine 3-Monooxygenase; D006867:Hydrolases; C021480:kynureninase