Disease relevance of quinolinic acid

• Quantitation of human immunodeficiency virus, immune activation factors, and quinolinic acid in AIDS brains [1].
• Plasma levels of quinolinic acid, a metabolic product of L-tryptophan via the kynurenine pathway, are reduced initially, and then become elevated when inflammation and fibrosis are more pronounced [2].
• The relationship between plasma and brain quinolinic acid levels and the severity of hepatic encephalopathy [3].
• Brain quinolinic acid concentrations are reportedly elevated in chronic liver failure [3].
• Brain quinolinic acid levels were elevated only in patients with acute liver failure and were uniformly distributed at concentrations below those observed in plasma [3].

Psychiatry related information on quinolinic acid

• Replication of the neurochemical characteristics of Huntington's disease by quinolinic acid [4].
• After treatment of AIDS dementia complex with zidovudine and treatment of the opportunistic infections with specific antimicrobial therapies, CSF levels of quinolinic acid decreased in parallel with clinical neurological improvement [5].
• Seven of eight animals exhibited motor skill impairment which was associated with elevated quinolinic acid in cerebrospinal fluid (CSF) [6].
• Although cerebrospinal fluid quinolinic acid levels were not different from controls, the ratio of quinolinic acid to kynurenic acid was significantly increased during the underweight phase of anorexia nervosa [7].
• The results show that quinolinic acid, an endogenous neuroexcitant, produces a deficit of cholinergic function similar to that described in the cortical tissue of patients with senile dementia of Alzheimer's type [8].

High impact information on quinolinic acid

• Human CNTF was found to exert a neuroprotective effect on several populations of striatal cells, including GABAergic, cholinergic and diaphorase-positive neurons which were all destined to die following administration of quinolinic acid [9].
• One week later, monkeys received unilateral injections of quinolinic acid into the previously implanted striatum to reproduce the neuropathology seen in Huntington's disease [9].
• No evidence for preservation of somatostatin-containing neurons after intrastriatal injections of quinolinic acid [10].
• Schwarcz and colleagues have shown that quinolinic acid (QA) can produce axon-sparing lesions similar to those observed in HD [4].
• The pathway includes two compounds, quinolinic acid and kynurenic acid, which are remarkably specific in their pharmacological profiles: one is a selective agonist at receptors sensitive to NMDA, whereas the other is a selective antagonist at low concentrations at the strychnine-resistant glycine modulatory site associated with the NMDA receptor [11].

Chemical compound and disease context of quinolinic acid

• In contrast to NTox, HIV-1 infection did not increase the release of the NMDA excitotoxin quinolinic acid (QUIN) from mononuclear cells [12].
• Finally, the capacity of the imaging method to detect distinct severity levels of striatal dopamine D2/D3 receptor loss was tested in a low, medium, and high dose quinolinic acid (QA) animal model of Huntington's disease [13].
• We assessed the ability of lithium to reduce neurodegeneration and to stimulate cell proliferation in a rat model of Huntington's disease in which quinolinic acid (QA) was unilaterally infused into the striatum [14].
• Neopterin and quinolinic acid are surrogate measures of disease activity in the juvenile idiopathic inflammatory myopathies [15].
• Accumulation of L-kynurenine and quinolinic acid (QUIN) in the brain occurs after either ischemic brain injury or after systemic administration of pokeweed mitogen [16].

Biological context of quinolinic acid

• Excitotoxic cell death stimulated by quinolinic acid injection into the striatum has a long history of "mimicking" many aspects of motor, behavioral, and neurochemical changes observed in Huntington's disease patients [17].
• Abnormalities of somatosensory evoked potentials in the quinolinic acid model of Huntington's disease: evidence that basal ganglia modulate sensory cortical input [18].
• It is suggested that decarboxylation of quinolinic acid gives rise to picolinic acid which is methylated to yield homarine [19].
• These results are consistent with the hypothesis that quinolinic acid accumulation in brain tissue contributes to atrophy in vulnerable brain regions in HIV infection and that virus replication is a significant driver of local quinolinic acid biosynthesis [20].
• RESULTS: A total of 1200 nmol/l quinolinic acid caused altered cell associations, a decrease in cell density and decreased microtubule-associated protein (MAP)-2 immunoreactivity compared with cultures exposed to 350 nmol/l quinolinic acid or controls [21].

Anatomical context of quinolinic acid

• CONCLUSIONS: The uniform distribution of quinolinic acid at subplasma concentrations in the brains of patients with acute liver failure suggests that it is synthesized peripherally and enters the brain across a permeabilized blood-brain barrier [3].
• IDO activity is linked with immunosuppression by its ability to inhibit lymphocyte proliferation, and with neurotoxicity through the generation of quinolinic acid and other toxins [22].
• Quinolinic acid-induced lesions of the hippocampus indicate that (+)3H-3-PPP labels hippocampal pyramidal cells and granule cells in the dentate gyrus [23].
• 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 [24].
• Intrastriatal injections of quinolinic acid decreased dramatically the levels of G(olf) alpha protein in the striatum and the substantia nigra, and those of G(olf) alpha mRNA in the striatum [25].

Associations of quinolinic acid with other chemical compounds

• KYNA-associated metabolites kynurenine, 3-hydroxykynurenine, and quinolinic acid were unchanged in the brain and liver of knockout mice. mKat-2(-/-) mice began to manifest hyperactivity and abnormal motor coordination at 2 weeks of age but were indistinguishable from wild type after 1 month of age [26].
• We conclude that local synthesis of quinolinic acid from L-tryptophan within the central nervous system follows the induction of indoleamine-2,3-dioxygenase, particularly within macrophage/microglia [27].
• Macaques that had recovered from D/1/California infection and were antibody positive and virus negative had normal CSF quinolinic acid and kynurenic acid concentrations [28].
• In order to explore the anatomical basis of possible functional interactions between glutamate and quinolinic acid in the rat striatum, pre- and postembedding immunocytochemical methods were used to localize 3HAO immunoreactivity (-i) and glutamate-i at the electron microscopic level [29].
• Compared to sham-operated control animals, quinolinic acid lesions of the pedunculopontine tegmental nucleus (PPTg) resulted in an attenuation of the stimulatory effects of intranigral neostigmine on DA efflux in the striatum [30].

Gene context of quinolinic acid

• QA produced degeneration of numerous medium-sized neurons, but not those enriched in Bcl-2-i. Many Bcl-2-i-enriched interneurons including those with CAT+ and PARV+ survived QA injection, while medium-sized neurons labeled for calbindin D-28K (CAL D-28+) did not [31].
• The present studies evaluated the potential contribution of Bcl-2, p53, and c-Myc to the differential vulnerability of striatal neurons to the excitotoxin quinolinic acid (QA) [31].
• Quinolinic acid upregulates chemokine production and chemokine receptor expression in astrocytes [32].
• We examined the effects of SF/HGF in comparison to acidic fibroblast growth factor-1 (FGF-1) on N-methyl-D-aspartate (NMDA) and quinolinic acid (QUIN)-induced excitotoxicity in primary cerebellar granule neurons [33].
• Quinolinic acid is an endogenous neurotoxin with NMDA receptor agonist properties [34].

Analytical, diagnostic and therapeutic context of quinolinic acid

• Quinolinic acid phosphoribosyltransferase: preferential glial localization in the rat brain visualized by immunocytochemistry [35].
• Intrastriatal injection of quinolinic acid (QA) in rats provides an animal model that mimics some of the neuropathological and neurochemical alterations observed in the striatum of patients with Huntington's disease (HD) [18].
• In the present study, we have explored the use of genetically modified neural stem cell lines producing nerve growth factor (NGF) or brain-derived neurotrophic factor (BDNF) as a means to protect the striatal neurons against excitotoxic damage after transplantation to the striatum, 1 week before the injection of quinolinic acid into the same area [36].
• The concentration of the endogenous excitotoxin quinolinic acid was determined in the cerebrospinal fluid of drug-free patients suffering from Huntington's disease or schizophrenia (control group) [37].
• CSF quinolinic acid levels are determined by local HIV infection: cross-sectional analysis and modelling of dynamics following antiretroviral therapy [38].

References