Document 0276
 DOCN  M9590276
 TI    Quinolinic acid toxicity in human brain cultures.
 DT    9509
 AU    Kerr SJ; Armati PJ; Brew BJ; Centre for Immunology, St Vincent's
       Hospital, Darlinghurst NSW.
 SO    Annu Conf Australas Soc HIV Med. 1994 Nov 3-6;6:246 (unnumbered poster).
       Unique Identifier : AIDSLINE ASHM6/95291823
 AB    Quinolinic acid (QUIN) is a excitotoxic tryptophan metabolite, that
       largely acts at the N-methyl-D-aspartate (NMDA) receptor. It has been
       implicated in the pathogenesis of a wide range of inflammatory
       neurological disorders, including the AIDS dementia complex (ADC).
       Although QUIN toxicity has been described in various animal models, to
       date there have been no reports of QUIN toxicity on human neurons. Brain
       tissue 14 and 17 weeks post-menstrual (WPM) was obtained from
       therapeutic terminations after informed consent. It was mechanically
       dissociated and plated out on 24 well culture plates at a density of 0.5
       X 10(6) cells/well. After 14 to 30 days in vitro (DIV), QUIN was added
       to replicate wells, and after 24 hours the supernatants were harvested
       and assayed for lactate dehydrogenase (LDH). Cells were observed
       regularly throughout the duration of the experiment. Initially,
       replicate wells of cells 14 WPM and 21 DIV, were treated with QUIN
       concentrations ranging from 0.5 microM to 1000 microM. No significant
       differences in LDH levels in the supernatants were noted in any of the
       cultures treated with QUIN compared to control cultures. Light
       microscopic analysis showed no observable morphological difference
       between QUIN treated cells and controls. Concentrations of QUIN ranging
       from 0.1mM to 10mM were also added to replicate cultures of tissue 17
       WPM. In four separate experiments on cells 14 to 28 DIV, the level of
       LDH in the supernatant were significantly above control levels for 5 and
       10mM QUIN concentrations. After 24 hours exposure to these
       concentrations, the cell bodies of affected neurons became rounded,
       processes had retracted, and some cells had detached from the
       substratum. These data provide information regarding the acute
       excitotoxicity of QUIN on human neurons.
 DE    Brain/*DRUG EFFECTS  Dose-Response Relationship, Drug  Fetus  Human
       Neurons/DRUG EFFECTS  Quinolinic Acid/*TOXICITY  Receptors,
       N-Methyl-D-Aspartate/*DRUG EFFECTS  Tissue Culture  MEETING ABSTRACT

       SOURCE: National Library of Medicine.  NOTICE: This material may be
       protected by Copyright Law (Title 17, U.S.Code).