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1996-02-27
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Document 0132
DOCN M9630132
TI Quinolinic acid levels in a murine retrovirus-induced immunodeficiency
syndrome.
DT 9603
AU Sei Y; Paul IA; Saito K; Layar R; Hartley JW; Morse HC 3rd; Skolnick P;
Heyes MP; Laboratory of Neuroscience, National Institute of Diabetes,;
Digestive and Kidney Diseases, National Institutes of Health,; Bethesda,
Maryland, USA.
SO J Neurochem. 1996 Jan;66(1):296-302. Unique Identifier : AIDSLINE
MED/96102947
AB Mice infected with the retrovirus mixture designated LP-BM5 murine
leukemia virus (MuLV) develop an immunosuppressive disease. Quinolinic
acid (QUIN) is an endogenous neurotoxic N-methyl-D-aspartate agonist
that may contribute to the pathogenesis of HIV-associated neurologic
disease. In the present study, the levels of QUIN in brain and blood
were measured in mice infected with LP-BM5 MuLV and compared with those
in uninfected mice and mice infected with the nonpathogenic strain of
ecotropic MuLV (helper component of LP-BM5 MuLV). Infection with LP-BM5
MuLV resulted in progressive increases in blood QUIN levels beginning 2
weeks after inoculation that peaked by 16 weeks postinfection. QUIN
levels were also increased in cerebral cortex, hippocampus, and
striatum. In systemic tissues, QUIN levels were increased in lung,
liver, and spleen. In contrast, infection with the ecotropic viral
component of the LP-BM5 MuLV mixture was not associated with any changes
in brain, blood, or systemic tissue QUIN levels, even though helper
virus burdens were comparable to those in mice infected with LP-BM5
MuLV. Treatment of LP-BM5 MuLV-infected mice with the antiretroviral
agent zidovudine (azidothymidine) significantly reduced blood and brain
QUIN levels in association with reductions in viral load in brain and
spleen. These observations suggest that elevated QUIN production is not
attributable to productive infection with retrovirus per se but occurs
in response to an agent or agents, such as cytokines, that are produced
by the host in response to virus infection.
DE Animal *AIDS Dementia Complex *Brain Chemistry Comparative Study
Cytokines/PHYSIOLOGY Defective Viruses/PATHOGENICITY *Disease Models,
Animal Helper Viruses/PATHOGENICITY Human Leukemia Viruses,
Murine/PATHOGENICITY Mice Mice, Inbred C57BL Murine Acquired
Immunodeficiency Syndrome/*METABOLISM Quinolinic Acid/*ANALYSIS/BLOOD
Viscera/CHEMISTRY JOURNAL ARTICLE
SOURCE: National Library of Medicine. NOTICE: This material may be
protected by Copyright Law (Title 17, U.S.Code).