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Cited by 19Tryptophan and brain disordersHIV Research and TreatmentNeuroinflammation and Neurodegeneration Mechanisms

Kynurenic Acid Metabolism in Various Types of Brain Pathology in HIV-1 Infected Patients

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Baran, H., Hainfellner, J.A., Kepplinger, B.·2012·International Journal of Tryptophan Research
DOI 10.4137/ijtr.s10627PMC PMC3528109
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Abstract

Kynurenic acid, an intermediate metabolite of L-kynurenine, is a competitive antagonist of inotropic excitatory amino acid (EAA) receptors as well as a non competitive antagonist of 7 alpha nicotine cholinergic receptors and its involvement in memory deficit and cognition impairment has been suggested. Alterations of kynurenic acid metabolism in the brain after HIV-1 (human immunodeficiency virus type-1) infection have been demonstrated. The present study evaluates the biosynthetic machinery of kynurenic acid e.g. the content of L-kynurenine and kynurenic acid, as well as the activity of enzymes synthesizing kynurenic acid, kynurenine aminotransferase I (KAT I) and kynurenine aminotransferase II (KAT II) in the frontal cortex and cerebellum of HIV-1 infected patients in relation to different types of pathology classified as follows: HIV in brain (HIV); opportunistic infection (OPP); infarction of brain (INF); malignant lymphoma of brain (LY); and glial dystrophy (GD) and of control (CO) subjects. Of all investigated pathologies the most frequent was OPP (65%), followed by HIV (26%), LY, INF, and GD (each 22%, respectively). Further, 68% of HIV-1 patients had bronchopneumonia, the highest incidence of which, at 60%, was seen in the OPP and LY group. Kynurenic acid was increased significantly in the frontal cortex of LY (392% of CO, P < 0.001), HIV (231% of CO, P < 0.01) and GD (193% of CO, P < 0.05), as well as in the cerebellum of GD (261% of CO, P < 0.01). A significant increase of L-kynurenine was observed in the frontal cortex of LY (385% of CO, P < 0.001) and INF (206% of CO, P < 0.01), and in the cerebellum of GD, LY, OPP and HIV (between 177% and 147% of CO). The KAT I activity increased significantly in the frontal cortex of all pathological subgroups, ie OPP = 420% > INF > LY > HIV > GD = 192% of CO. In the cerebellum, too, all pathological subgroups showed marked increase of KAT I activity (OPP = 320% > LY, HIV > GD > INF = 176% of CO). On contrary, the activity of KAT II was moderately, but significantly, higher in the frontal cortex of INF and OPP; in the cerebellum of HIV, OPP and LY it was comparable to the control, while mildly reduced in INF and GD. Interestingly, normal subjects with the diagnosis of bronchopneumonia were characterized by high kynurenic acid metabolism in the brain, too. Correlation analyses between kynurenine parameters revealed association between high ratio KAT I/KAT II and increased kynurenic acid level and lower L-kynurenine in the frontal cortex and cerebellum of HIV and LY subgroups. The present study revealed a different pattern of alteration of kynurenic acid metabolism in frontal cortex and cerebellum among investigated pathological subgroups of HIV-1 infected patients. Interestingly, a marked enhancement of kynurenic acid metabolism in the brain has been found with occurrence of bronchopneumonia. This finding indicates a notable association between impaired conditions of oxygen availability and enhancement of kynurenic acid formation in the human brain. These observation(s) might have an impact on the understanding of pathological processes in the brain after HIV-1 infection involving the development of neuropsychiatric and neurological symptoms, including memory and cognition impairment.

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Authors
Baran, H., Hainfellner, J. A., & Kepplinger, B.
Affiliations
  • University of Vienna (AT)
  • SeneCura Kliniken und Heime (Austria) (AT)
Corresponding author
Baran, H.
ORCID
Venue
International Journal of Tryptophan Research
Publisher
SAGE Publications
Published
2012-01
Volume
5
Pages
49-64
ISSN
1178-6469 (ISSN-L)
DOI
10.4137/ijtr.s10627
PMC
PMC3528109
OpenAlex
W2092875932
Cited by
19
References
52
Citations by year
2026: 1 · 2025: 1 · 2024: 1 · 2023: 1 · 2022: 3 · 2021: 4 · 2017: 1 · 2016: 2 · 2015: 1 · 2014: 3 · 2013: 1
FWCI
0.49
Type
journal article
Language
en
Open access
Licence
Locations
  • International Journal of Tryptophan Research (publishedVersion, cc-by-nc)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Topics
  • Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
  • Life Sciences › Immunology and Microbiology › Virology › HIV Research and Treatment
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
Keywords
kynurenic acid, L-kynurenine, kynurenine aminotransferase I, kynurenine aminotransferase II, HIV-1 infection, neuropathology, opportunistic infections, cerebral infarction, brain lymphoma, frontal cortex, cerebellum, glutamate receptors, nicotinic acetylcholine receptors

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