A hypothetical astrocyte–microglia lactate shuttle derived from a 1H NMR metabolomics analysis of cerebrospinal fluid from a cohort of South African children with tuberculous meningitis

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• 作者：Shayne Mason ; A. Marceline van Furth ; Lodewyk J. Mienie ; Udo F. H. Engelke…
• 关键词：Tuberculous meningitis (TBM) ; Cerebrospinal fluid (CSF) ; Nuclear magnetic resonance (NMR) metabolomics ; “Astrocyte–microglia lactate shuttle-(AMLS) hypothesis
• 刊名：Metabolomics
• 出版年：2015
• 出版时间：August 2015
• 年：2015
• 卷：11
• 期：4
• 页码：822-837
• 全文大小：1,538 KB
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• 作者单位：Shayne Mason (1)
  A. Marceline van Furth (2)
  Lodewyk J. Mienie (3)
  Udo F. H. Engelke (4)
  Ron A. Wevers (4)
  Regan Solomons (5)
  Carolus J. Reinecke (1)
  
  1. Centre for Human Metabonomics, Faculty of Natural Sciences, North-West University (Potchefstroom Campus), Private Bag X6001, Potchefstroom, 2531, South Africa
  2. Department of Paediatric Infectious Diseases–Immunology and Rheumatology, Vrije Universiteit Medical Centre, De Boelelaan 1117, 1081, HV, Amsterdam, The Netherlands
  3. Potchefstroom Laboratory for Inborn Errors of Metabolism, Division for Biochemistry, North-West University (Potchefstroom Campus), Private Bag X6001, Potchefstroom, South Africa
  4. Department of Laboratory Medicine, Radboud University Nijmegen Medical Centre, PO Box 9101, 6500, HB, Nijmegen, The Netherlands
  5. Department of Paediatrics and Child Health, Faculty of Medicine and Health Sciences, Stellenbosch University, PO Box 19063, Tygerberg, 7505, South Africa
  
• 刊物主题：Biochemistry, general; Molecular Medicine; Cell Biology; Developmental Biology; Biomedicine general;
• 出版者：Springer US
• ISSN：1573-3890

文摘

Tuberculosis meningitis (TBM) is the most severe form of extra-pulmonary tuberculosis and is particularly intense in small children; there is no universally accepted algorithm for the diagnosis and substantiation of TB infection, which can lead to delayed intervention, a high risk factor for morbidity and mortality. In this study a proton magnetic resonance (1H NMR)-based metabolomics analysis and several chemometric methods were applied to data generated from lumber cerebrospinal fluid (CSF) samples from three experimental groups: (1) South African infants and children with confirmed TBM, (2) non-meningitis South African infants and children as controls, and (3) neurological controls from the Netherlands. A total of 16 NMR-derived CSF metabolites were identified, which clearly differentiated between the controls and TBM cases under investigation. The defining metabolites were the combination of perturbed glucose and highly elevated lactate, common to some other neurological disorders. The remaining 14 metabolites of the host’s response to TBM were likewise mainly energy-associated indicators. We subsequently generated a hypothesis expressed as an “astrocyte–microglia lactate shuttle-(AMLS) based on the host’s response, which emerged from the NMR-metabolomics information. Activation of microglia, as implied by the AMLS hypothesis, does not, however, present a uniform process and involves intricate interactions and feedback loops between the microglia, astrocytes and neurons that hamper attempts to construct basic and linear cascades of cause and effect; TBM involves a complex integration of the responses from the various cell types present within the CNS, with microglia and the astrocytes as main players.