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
Date
2015Author
Mason, Shayne
Mienie, Lodewyk J.
Reinecke, Carolus J.
Van Furth, A. Marceline
Engelke, Udo F.H.
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Show full item recordAbstract
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
URI
http://hdl.handle.net/10394/18540https://doi.org/10.1007/s11306-014-0741-z
https://link.springer.com/article/10.1007%2Fs11306-014-0741-z