Age-Related Increase of Kynurenic Acid in Human Cerebrospinal Fluid – IgG and β2-Microglobulin Changes

• Published in: Neuro-Signals Vol. 14; no. 3; pp. 126 - 135
• Main Authors: Kepplinger, Berthold, Baran, Halina, Kainz, Astrid, Ferraz-Leite, Heber, Newcombe, Jea, Kalina, Pavol
• Format: Journal Article
• Language: English
• Published: Basel, Switzerland 29.07.2005
• Subjects: Original Paper; IgG; Cerebrospinal fluid; Kynurenic acid; Ageing; β2-Microglobulin
• ISSN: 1424-862X; 1424-8638
• DOI: 10.1159/000086295

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 β 2 -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 β 2 -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 β 2 -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.