Cerebral Acetate Metabolism: Towards Its In Vivo Assessment

Abstract

AbstractAcetate as precursor and tracer for cerebral metabolism has received high interest since the late 1950s when it was first shown with radiolabels that, among others, acetate incorporates very differently into cerebral metabolites than glucose. Subsequent work has taken advantage of acetate’s exclusive cerebral uptake into glial cells in order to probe metabolic compartmentation and the interplay of the intricately and inextricably intermingled glial and neuronal tissues in intact brain. The present review takes a three-pronged approach to outline the current understanding of cerebral acetate uptake, metabolism and the learning derived thereof with regard to the integral metabolism in mammalian brain. (1) Acetate-based tracer modalities including radiography, positron emission tomography (PET) and magnetic resonance spectroscopy (MRS) together with corresponding labelling concepts ranging from specific (radio-)activity to advanced multi-labelling strategies used for assessing cerebral metabolism are presented. (2) Translational aspects and efforts in moving the assessment of cerebral acetate metabolism from cell cultures and ex vivo tissue toward its non-invasive detection in situ in the brain of living animals and man are then discussed. (3) The original notion of cerebral substrate selection is complemented with current data on metabolic compartmentation and substrate trafficking to build a comprehensive, though in part still controversial view on cerebral metabolism. A collective of studies, which have utilised acetate to explore cerebral metabolism in health and disease, are put into perspective with this latter notion. Metabolism in brain tumours and cerebral ischemia as well as alterations in cerebral metabolism brought about by primarily extra-cerebral disorders such as diabetes and thyroid hormone deficits are discussed. Finally, acetate’s involvement in psychiatric and neurological disorders receives particular focus as this area is largely dominated by newer work addressing neurotransmitter balances and receptor involvement from a glial stance and is offering potential links to functional and behavioural data.Keywords11C13C14C2H3HIsotopeIsotopomerLabellingMagnetic resonance spectroscopyMRSPositron emission tomographyPETMass-spectrometryMSAstrocyteGliaNeuronAcetateGlutamateGlutamineTricarboxylicacid cycleCell cultureMouseRatMonkeyManDiabetesEpilepsySchizophreniaStroke