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Age-related increase of kynurenic acid in human cerebrospinal fluid-IgG and beta(2)-microglobulin changes

Kepplinger, B; Baran, H; Kainz, A; Ferraz-Leite, H; Newcombe, J; Kalina, P; (2005) Age-related increase of kynurenic acid in human cerebrospinal fluid-IgG and beta(2)-microglobulin changes. Neurosignals , 14 (3) 126 - 135. 10.1159/000086295. Green open access

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Abstract

Kynurenic acid (KYNA) is an endogenous metabolite in the kynurenine pathway of tryptophan degradation and is an antagonist at the glycine site of the N-methyl-D-aspartate as well as at the alpha 7 nicotinic cholinergic receptors. In the brain tissue KYNA is synthesised from L-kynurenine by kynurenine aminotransferases (KAT) I and II. A host of immune mediators influence tryptophan degradation. In the present study, the levels of KYNA in cerebrospinal fluid (CSF) and serum in a group of human subjects aged between 25 and 74 years were determined by using a high performance liquid chromatography method. In CSF and serum KAT I and II activities were investigated by radioenzymatic assay, and the levels of β2-microglobulin, a marker for cellular immune activation, were determined by ELISA. The correlations between neurochemical and biological parameters were evaluated. Two subject groups with significantly different ages, i.e. <50 years and >50 years, p < 0.001, showed statistically significantly different CSF KYNA levels, i.e. 2.84 ± 0.16 fmol/μl vs. 4.09 ± 0.14 fmol/μl, p < 0.001, respectively; but this difference was not seen in serum samples. Interestingly, KYNA is synthesised in CSF principally by KAT I and not KAT II, however no relationship was found between enzyme activity and ageing. A positive relationship between CSF KYNA levels and age of subjects indicates a 95% probability of elevated CSF KYNA with ageing (R = 0.6639, p = 0.0001). KYNA levels significantly correlated with IgG and β2-microglobulin levels (R = 0.5244, p = 0.0049; R = 0.4253, p = 0.043, respectively). No correlation was found between other biological parameters in CSF or serum. In summary, a positive relationship between the CSF KYNA level and ageing was found, and the data would suggest age-dependent increase of kynurenine metabolism in the CNS. An enhancement of CSF IgG and β2-microglobulin levels would suggest an activation of the immune system during ageing. Increased KYNA metabolism may be involved in the hypofunction of the glutamatergic and/or nicotinic cholinergic neurotransmission in the ageing CNS.

Type: Article
Title: Age-related increase of kynurenic acid in human cerebrospinal fluid-IgG and beta(2)-microglobulin changes
Open access status: An open access version is available from UCL Discovery
DOI: 10.1159/000086295
Publisher version: http://dx.doi.org/10.1159/000086295
Language: English
Additional information: From an open access publication from Karger
Keywords: Ageing, Cerebrospinal fluid, Kynurenic acid, Igg, beta(2)-microglobulin, Performance liquid-chromatography, Quinolinic acid, Rat-brain, Aminotransferase-i, Neuroactive kynurenines, Neurological disorders, Huntingtons-disease, Alzheimers-disease, Oxidative stress, Reference values
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Neuroinflammation
URI: https://discovery.ucl.ac.uk/id/eprint/20841
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