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ORIGINAL RESEARCH article

Front. Neurosci.
Sec. Neuroenergetics and Brain Health
Volume 18 - 2024 | doi: 10.3389/fnins.2024.1270041
This article is part of the Research Topic NMR insights into Natural Product Chemistry View all articles

1H-NMR metabolomics investigation of CSF from children with HIV reveals altered neuroenergetics due to persistent immune activation

Provisionally accepted
Anicia Thirion¹ Anicia Thirion¹ 1Du Toit Loots Du Toit Loots 1Monray E. Williams Monray E. Williams 1Regan Solomons Regan Solomons 2Shayne Mason Shayne Mason 1*
  • 1 North-West University, Potchefstroom, North West, South Africa
  • 2 Stellenbosch University, Stellenbosch, Western Cape, South Africa

The final, formatted version of the article will be published soon.

    Background: HIV can invade the central nervous system (CNS) early during infection, invading perivascular macrophages and microglia, which in turn release viral particles and immune mediators that dysregulate all brain cell types. Consequently, children living with HIV often present with neurodevelopmental delays. Methods: In this study, we used proton nuclear magnetic resonance (1H-NMR) spectroscopy to analyze the neurometabolic profile of HIV infection using cerebrospinal fluid samples obtained from 17 HIV+ and 50 HIV- South African children. Results: Nine metabolites, including glucose, lactate, glutamine, 1,2-propanediol, acetone, 3-hydroxybutyrate, acetoacetate, 2-hydroxybutyrate, and myo-inositol, showed significant differences when comparing children infected with HIV and those uninfected. These metabolites may be associated with activation of the innate immune response and disruption of neuroenergetics pathways. Conclusion: These results elucidate the neurometabolic state of children infected with HIV, including upregulation of glycolysis, dysregulation of ketone body metabolism, and elevated reactive oxygen species production. Furthermore, we hypothesize that neuroinflammation alters astrocyte-neuron communication, lowering neuronal activity in children infected with HIV, which may contribute to the neurodevelopmental delay often observed in this population.

    Keywords: pediatric, HIV - human immunodeficiency virus, CSF (cerebrospinal fluid), HIV-associated neurocognitive disorder (HAND), Proton nuclear magnetic resonance (1H NMR) spectroscopy, Metabolomics, Neuroenergetics

    Received: 31 Jul 2023; Accepted: 15 Apr 2024.

    Copyright: © 2024 Thirion¹, Loots, Williams, Solomons and Mason. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Shayne Mason, North-West University, Potchefstroom, 2520, North West, South Africa

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