Kynurenic acid metabolism in the brain of HIV-1 infected patients

2000 ◽  
Vol 107 (10) ◽  
pp. 1127-1138 ◽  
Author(s):  
H. Baran ◽  
J. A. Hainfellner ◽  
B. Kepplinger ◽  
P. R. Mazal ◽  
H. Schmid ◽  
...  
Keyword(s):  
Kynurenic Acid ◽  
Acid Metabolism ◽  
The Brain ◽  
Hiv 1

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

2012 ◽  
Vol 5 ◽  
pp. IJTR.S10627 ◽  
Author(s):  
H. Baran ◽  
J.A. Hainfellner ◽  
B. Kepplinger
Keyword(s):  
Frontal Cortex ◽  
Kynurenic Acid ◽  
Acid Metabolism ◽  
Excitatory Amino Acid ◽  
High Ratio ◽  
Competitive Antagonist ◽  
Kynurenine Aminotransferase ◽  
Cognition Impairment ◽  
The Brain ◽  
Hiv 1

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.

scholarly journals Association between fatty acid metabolism in the brain and Alzheimer disease neuropathology and cognitive performance: A nontargeted metabolomic study

PLoS Medicine ◽  
2017 ◽  
Vol 14 (3) ◽  
pp. e1002266 ◽  
Author(s):  
Stuart G. Snowden ◽  
Amera A. Ebshiana ◽  
Abdul Hye ◽  
Yang An ◽  
Olga Pletnikova ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Alzheimer Disease ◽  
Cognitive Performance ◽  
Fatty Acid Metabolism ◽  
Acid Metabolism ◽  
The Brain ◽  
Metabolomic Study

scholarly journals Imaging Upregulated Brain Arachidonic Acid Metabolism in HIV-1 Transgenic Rats

2015 ◽  
Vol 35 (8) ◽  
pp. 1386-1386
Author(s):  
Mireille Basselin ◽  
Epolia Ramadan ◽  
Miki Igarashi ◽  
Lisa Chang ◽  
Mei Chen ◽  
...  
Keyword(s):  
Arachidonic Acid ◽  
Acid Metabolism ◽  
Arachidonic Acid Metabolism ◽  
Transgenic Rats ◽  
Hiv 1

scholarly journals The Brain Metabolite Kynurenic Acid Inhibits α7 Nicotinic Receptor Activity and Increases Non-α7 Nicotinic Receptor Expression: Physiopathological Implications

2001 ◽  
Vol 21 (19) ◽  
pp. 7463-7473 ◽  
Author(s):  
Corey Hilmas ◽  
Edna F. R. Pereira ◽  
Manickavasagom Alkondon ◽  
Arash Rassoulpour ◽  
Robert Schwarcz ◽  
...  
Keyword(s):  
Nicotinic Receptor ◽  
Kynurenic Acid ◽  
Receptor Expression ◽  
Receptor Activity ◽  
Brain Metabolite ◽  
The Brain

scholarly journals HIV-1 and chemokines in the brain: location, location—location?

1999 ◽  
Vol 4 (3) ◽  
pp. 203-205 ◽  
Author(s):  
P B Tran ◽  
O Meucci ◽  
R J Miller
Keyword(s):  
The Brain ◽  
Hiv 1

scholarly journals The HIV-1 Transgenic Rat: Relevance for HIV Noninfectious Comorbidity Research

2020 ◽  
Vol 8 (11) ◽  
pp. 1643
Author(s):  
Frank Denaro ◽  
Francesca Benedetti ◽  
Myla D. Worthington ◽  
Giovanni Scapagnini ◽  
Christopher C. Krauss ◽  
...  
Keyword(s):  
Neuronal Degeneration ◽  
Cell Types ◽  
Transgenic Rat ◽  
Specific Cell ◽  
Rat Tissues ◽  
Local Production ◽  
Specific Tissue ◽  
Effective Models ◽  
The Brain ◽  
Hiv 1

HIV noninfectious comorbidities (NICMs) are a current healthcare challenge. The situation is further complicated as there are very few effective models that can be used for NICM research. Previous research has supported the use of the HIV-1 transgenic rat (HIV-1TGR) as a model for the study of HIV/AIDS. However, additional studies are needed to confirm whether this model has features that would support NICM research. A demonstration of the utility of the HIV-1TGR model would be to show that the HIV-1TGR has cellular receptors able to bind HIV proteins, as this would be relevant for the study of cell-specific tissue pathology. In fact, an increased frequency of HIV receptors on a specific cell type may increase tissue vulnerability since binding to HIV proteins would eventually result in cell dysfunction and death. Evidence suggests that observations of selective cellular vulnerability in this model are consistent with some specific tissue vulnerabilities seen in NICMs. We identified CXCR4-expressing cells in the brain, while specific markers for neuronal degeneration demonstrated that the same neural types were dying. We also confirm the presence of gp120 and Tat by immunocytochemistry in the spleen, as previously reported. However, we observed very rare positive cells in the brain. This underscores the point that gp120, which has been reported as detected in the sera and CSF, is a likely source to which these CXCR4-positive cells are exposed. This alternative appears more probable than the local production of gp120. Further studies may indicate some level of local production, but that will not eliminate the role of receptor-mediated pathology. The binding of gp120 to the CXCR4 receptor on neurons and other neural cell types in the HIV-1TGR can thus explain the phenomena of selective cell death. Selective cellular vulnerability may be a contributing factor to the development of NICMs. Our data indicate that the HIV-1TGR can be an effective model for the studies of HIV NICMs because of the difference in the regional expression of CXCR4 in rat tissues, thus leading to specific organ pathology. This also suggests that the model can be used in the development of therapeutic options.

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