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Titolo:
SOURCES OF THE NEUROTOXIN QUINOLINIC ACID IN THE BRAIN OF HIV-1-INFECTED PATIENTS AND RETROVIRUS-INFECTED MACAQUES
Autore:
HEYES MP; SAITO K; LACKNER A; WILEY CA; ACHIM CL; MARKEY SP;
Indirizzi:
NIMH,LAB NEUROTOXICOL,BLDG 10,ROOM 3D40,9000 ROCKVILLE PIKE BETHESDA MD 20892 HARVARD UNIV,SCH MED,NEW ENGLAND REG PRIMATE RES CTR SOUTHBOROUGH MA 01772 PRESBYTERIAN UNIV HOSP,DIV NEUROPATHOL PITTSBURGH PA 15213
Titolo Testata:
The FASEB journal
fascicolo: 10, volume: 12, anno: 1998,
pagine: 881 - 896
SICI:
0892-6638(1998)12:10<881:SOTNQA>2.0.ZU;2-3
Fonte:
ISI
Lingua:
ENG
Soggetto:
HUMAN-IMMUNODEFICIENCY-VIRUS; KYNURENINE PATHWAY METABOLITES; COMPLEX PARTIAL SEIZURES; CENTRAL-NERVOUS-SYSTEM; CONVERT L-TRYPTOPHAN; CEREBROSPINAL-FLUID; NEUROLOGICAL DISEASE; IMMUNE ACTIVATION; NEUROACTIVE KYNURENINES; CEREBRAL-ISCHEMIA;
Keywords:
MACROPHAGES; ASTROCYTES; INDOLEAMINE-2,3-DIOXYGENASE; KYNURENINE-3-HYDROXYLASE; KYNURENINASE; KYNURENINE AMINOTRANSFERASE; L-TRYPTOPHAN; L-KYNURENINE; KYNURENIC ACID; RETROVIRUS; BLOOD-BRAIN BARRIER; CYTOKINES; NONHUMAN PRIMATES;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Science Citation Index Expanded
Science Citation Index Expanded
Citazioni:
71
Recensione:
Indirizzi per estratti:
Citazione:
M.P. Heyes et al., "SOURCES OF THE NEUROTOXIN QUINOLINIC ACID IN THE BRAIN OF HIV-1-INFECTED PATIENTS AND RETROVIRUS-INFECTED MACAQUES", The FASEB journal, 12(10), 1998, pp. 881-896

Abstract

This: study investigated the sources of quinolinic acid, a neurotoxictryptophan-kynurenine pathway metabolite, in the brain and blood of HIV-infected patients and retrovirus-infected macaques.In brain, quinolinic acid concentrations in HIV-infected patients were elevated by >300-fold to concentrations that exceeded cerebrospinal fluid (CSF) by 8.9-fold. There were no significant correlations between elevated serum quinolinic acid levels with those in CSF and brain parenchyma. Becausenonretrovirus-induced encephalitis confounds the interpretation of human postmortem data, rhesus macaques infected with retrovirus were used to examine the mechanisms of increased quinolinic acid accumulationsand determine the relationships of quinolinic acid to encephalitits and systemic responses. The largest kynurenine pathway responses in brain were associated with encephalitis and were independent of systemic responses. CSF quinolinic acid levels were also elevated in all infected macaques, but particularly those with retrovirus-induced encephalitis. In contrast to the brain changes, there was no difference in any systemic measure between macaques with encephalitis: vs. those without. Direct measures of the amount of quinolinic acid in brain derived from blood in a macaque with encephalitis showed that almost all quinolinic acid (>98%) was synthesized locally within the brain. These resultsdemonstrate a role for induction of indoleamine-2,3-dioxygenase in accelerating the local formation of quinolinic acid within the brain tissue, particularly in areas of encephalitis, rather than entry of quinolinic acid into the brain from the meninges or blood. Strategies to reduce QUIN production, targeted at intracerebral sites, are potential approaches to therapy.-Heyes, M. P., Saito, K., Lackner, A., Wiley, C. A., Achim, C. L., Markey, S. P. Sources of the neurotoxin quinolinic acid in the brain of HIV-l-infected patients and retrovirus-infected macaques.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 06/04/20 alle ore 01:38:31