Quinolinic acid in cerebrospinal fluid and serum in HIV‐1 Infection: Relationship to clinical and neurological status

Abstract

Quinolinic acid is an "excitotoxic" metabolite and an agonist of N-methyl-D-aspartate receptors. Of patients infected with human immunodeficiency virus type 1 (HIV-1) who were neurologically normal or exhibited only equivocal and subclinical signs of the acquired immunodeficiency syndrome (AIDS) dementia complex, concentrations of quinolinic acid in cerebrospinal fluid (CSF) were increased twofold in patients in the early stages of disease (Walter Reed stages 1 and 2) and averaged 3.8 times above normal in later-stage patients (Walter Reed stages 4 through 6). However, in patients with either clinically overt AIDS dementia complex, aseptic meningitis, opportunistic infections, or neoplasms, CSF levels were elevated over 20-fold and generally paralleled the severity of cognitive and motor dysfunction. CSF concentrations of quinolinic acid were significantly correlated to the severity of the neuropsychological deficits. 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. By analysis of the relationship between levels of quinolinic acid in the CSF and serum and integrity of the blood-brain barrier, as measured by the CSF:serum albumin ratio, it appears that CSF levels of quinolinic acid may be derived predominantly from intracerebral sources and perhaps from the serum. While quinolinic acid may be another "marker" of host- and virus-mediated events in the brain, the established excitotoxic effects of quinolinic acid and the magnitude of the increases in CSF levels of the acid raise the possibility that quinolinic acid plays a direct role in the pathogenesis of brain dysfunction associated with HIV-1 infection.

The immune-mediated alteration of serotonin and glutamate: towards an integrated view of depression

“…An increase of quinolinic acid is strongly associated with several prominent features of depression: decrease in reaction time [29][30][31] and cognitive deficits, in particular difficulties in learning. 32 In an animal model, an increase of quinolinic acid and 3-hydroxykynurenine was shown to be associated with anxiety.…”

Métodos de preparação e atividade biológica do ácido quinolínico e derivados

“…Supõe-se que um destes agentes neurotóxicos seja o ácido quinolínico 6 (Esquema 1). Este composto endogênico, produto da degradação enzimática do triptofano 1, é de concentração particularmente elevada no líquido céfalo-raquidiano de pacientes portadores da AIDS 3 . Além desta evidência, o aumento da taxa de ácido quinolínico resulta em um forte aumento da taxa de cálcio nos neurônios, devido à sua interação direta ou indireta com o receptor ácido-N-metil-Daspártico (NMDA) [4][5][6] , uma das sub-classes dos receptores do glutamato no cérebro.…”

Potentiation of excitotoxicity in HIV-1-associated Dementia and the significance of glutaminase

“…Improper regulation of these factors can lead to impaired cellular functioning, modified neurotransmitter action, amplified inflammation and neuronal damage. Various potential neurotoxins are generated and released during the inflammatory process including reactive oxygen species, tumor necrosis factor-α (TNF-α), arachidonic acid, platelet-activating factor (PAF), nitric oxide, quinolinic acid, and glutamate (20,30,(46)(47)(48)(49)(50)(51)(52).…”