Alterations in glutamate, arginine, and energy metabolism characterize cerebrospinal fluid and plasma metabolome of persons with HIV-associated dementia.
Details
Serval ID
serval:BIB_E10D6B785AB6
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Alterations in glutamate, arginine, and energy metabolism characterize cerebrospinal fluid and plasma metabolome of persons with HIV-associated dementia.
Journal
AIDS
ISSN
1473-5571 (Electronic)
ISSN-L
0269-9370
Publication state
Published
Issued date
01/03/2024
Peer-reviewed
Oui
Volume
38
Number
3
Pages
299-308
Language
english
Notes
Publication types: Journal Article
Publication Status: ppublish
Publication Status: ppublish
Abstract
HIV-associated dementia (HAD) is the most severe clinical expression of HIV-mediated neuropathology, and the processes underlying its development remain poorly understood. We aimed to exploit high-dimensional metabolic profiling to gain insights into the pathological mechanisms associated to HAD.
In this cross-sectional study, we utilized metabolomics to profile matched cerebrospinal fluid (CSF) and plasma samples of HAD individuals ( n = 20) compared with neurologically asymptomatic people with HIV (ASYM, n = 20) and healthy controls (NEG, n = 20).
Identification of plasma and CSF metabolites was performed by liquid-chromatography or gas-chromatography following a validated experimental pipeline. The resulting metabolic profiles were analyzed by machine-learning algorithms, and altered pathways were identified by comparison with KEGG pathway database.
In CSF, HAD patients displayed an imbalance in glutamine/glutamate ratio, decreased levels of isocitrate and arginine, and increased oxidative stress when compared with ASYM or NEG. These changes were confirmed in matched plasma samples, which in addition revealed an accumulation of eicosanoids and unsaturated fatty acids in HAD individuals. Pathway analysis in both biological fluids suggested that alterations in several metabolic processes, including protein biosynthesis, glutamate and arginine metabolism, and energy metabolism, in association to a perturbed eicosanoid metabolism in plasma, may represent the metabolic signature associated to HAD.
These findings show that HAD may be associated with metabolic modifications in CSF and plasma. These preliminary data may be useful to identify novel metabolic biomarkers and therapeutic targets in HIV-associated neurological impairment.
In this cross-sectional study, we utilized metabolomics to profile matched cerebrospinal fluid (CSF) and plasma samples of HAD individuals ( n = 20) compared with neurologically asymptomatic people with HIV (ASYM, n = 20) and healthy controls (NEG, n = 20).
Identification of plasma and CSF metabolites was performed by liquid-chromatography or gas-chromatography following a validated experimental pipeline. The resulting metabolic profiles were analyzed by machine-learning algorithms, and altered pathways were identified by comparison with KEGG pathway database.
In CSF, HAD patients displayed an imbalance in glutamine/glutamate ratio, decreased levels of isocitrate and arginine, and increased oxidative stress when compared with ASYM or NEG. These changes were confirmed in matched plasma samples, which in addition revealed an accumulation of eicosanoids and unsaturated fatty acids in HAD individuals. Pathway analysis in both biological fluids suggested that alterations in several metabolic processes, including protein biosynthesis, glutamate and arginine metabolism, and energy metabolism, in association to a perturbed eicosanoid metabolism in plasma, may represent the metabolic signature associated to HAD.
These findings show that HAD may be associated with metabolic modifications in CSF and plasma. These preliminary data may be useful to identify novel metabolic biomarkers and therapeutic targets in HIV-associated neurological impairment.
Keywords
Humans, Arginine/metabolism, Glutamic Acid/metabolism, Glutamic Acid/therapeutic use, Cross-Sectional Studies, HIV Infections/complications, HIV Infections/drug therapy, Metabolome, Metabolomics/methods, AIDS Dementia Complex, Energy Metabolism, Biomarkers
Pubmed
Web of science
Open Access
Yes
Create date
07/02/2024 17:09
Last modification date
02/03/2024 8:10