title: Sustained increases in cerebrospinal fluid quinolinic acid concentrations in rhesus macaques (Macaca mulatta) naturally infected with simian retrovirus type-D.
abstract: Sustained increases in CSF concentrations of the excitotoxin quinolinic acid (QUIN) occur in patients with AIDS and have been implicated in the pathogenesis of the AIDS dementia complex. Macaques in captivity may also develop immunodeficiency syndromes caused by retrovirus infection, including simian retrovirus type-D. In the present study, CSF QUIN concentrations were moderately increased in retrovirus type-D-positive/antibody-negative macaques (163.8 +/- 35.1 nmol/l; P less than 0.0001, n = 21) but not virus-negative/antibody-positive macaques (27.4 +/- 9.4 nmol/l, n = 8) compared to uninfected control macaques (23.0 +/- 1.6 nmol/l; n = 22). CSF QUIN concentrations in virus-positive/antibody-negative macaques tended to remain elevated over a 4-20 month period. Post-mortem studies of 9 virus-positive/antibody-negative macaques and 6 virus-negative/antibody-positive macaques revealed inflammatory responses in the brains of 6 of 9 virus-positive/antibody negative macaques, including lymphocytic infiltrates of the choroid plexus in 3 macaques, glial nodules in 3 macaques and perivascular infiltrates in 1 macaque. These lesions were not extensive and no evidence of brain atrophy was observed. No lesions were observed in the 6 antibody-positive/virus-negative macaques. Small increases in plasma L-kynurenine in virus-positive/antibody-negative macaques are consistent with activation of indoleamine-2,3-dioxygenase, the first enzyme in the kynurenine pathway. We conclude that sustained moderate increases in CSF QUIN occur in viremic simian retrovirus type-D macaques. The increases in CSF QUIN may reflect inflammatory responses within the brain or synthesis of QUIN precursors in systemic tissues, their entry into brain and subsequent conversion to QUIN. The neuropathologic significance of these increases in CSF QUIN remains to be determined.
authors.affiliation: Section on Analytical Biochemistry, NIMH, Bethesda, MD 20892.
authors.forename: M P
authors.initials: MP
authors.lastname: Heyes
authors.forename: M
authors.initials: M
authors.lastname: Gravell
authors.forename: W T
authors.initials: WT
authors.lastname: London
authors.forename: M
authors.initials: M
authors.lastname: Eckhaus
authors.forename: J H
authors.initials: JH
authors.lastname: Vickers
authors.forename: J A
authors.initials: JA
authors.lastname: Yergey
authors.forename: M
authors.initials: M
authors.lastname: April
authors.forename: D
authors.initials: D
authors.lastname: Blackmore
authors.forename: S P
authors.initials: SP
authors.lastname: Markey
mesh_terms: D000818:Animals; D001921:Brain / Q000382:microbiology / Q000473:pathology; D007736:Kynurenic Acid / Q000097:blood; D008253:Macaca mulatta; D017378:Quinolinic Acid; D011805:Quinolinic Acids / Q000097:blood / Q000134:cerebrospinal fluid*; D012016:Reference Values; D015301:Retroviruses, Simian / Q000302:isolation & purification; D016097:Simian Acquired Immunodeficiency Syndrome / Q000097:blood / Q000134:cerebrospinal fluid* / Q000382:microbiology; D014364:Tryptophan / Q000097:blood
chemical_list: D011805:Quinolinic Acids; D014364:Tryptophan; D017378:Quinolinic Acid; D007736:Kynurenic Acid