Setting standards for brain collection procedures in metabolomic studies.

Current metabolomics technologies can measure hundreds of chemical entities in tissue extracts with good reliability. However, long-recognized requirements to halt enzyme activities during the initial moments of sample preparation are usually overlooked, allowing marked postmortem shifts in levels of labile metabolites representing diverse pathways. In brain many such changes occur in a matter of seconds.

Does hyperphenylalaninemia induce brain glucose hypometabolism? Cerebral spinal fluid findings in treated adult phenylketonuric patients.

Despite numerous studies in human patients and animal models for phenylketonuria (PKU; OMIM#261600), the pathophysiology of PKU and the underlying causes of brain dysfunction and cognitive problems in PKU patients are not well understood. In this study, lumbar cerebral spinal fluid (CSF) was obtained immediately after blood sampling from early-treated adult PKU patients who had fasted overnight. Metabolite and amino acid concentrations in the CSF of PKU patients were compared with those of non-PKU controls.

Brain energy metabolism: A roadmap for future research.

Although we have learned much about how the brain fuels its functions over the last decades, there remains much still to discover in an organ that is so complex. This article lays out major gaps in our knowledge of interrelationships between brain metabolism and brain function, including biochemical, cellular, and subcellular aspects of functional metabolism and its imaging in adult brain, as well as during development, aging, and disease. The focus is on unknowns in metabolism of major brain substrates and associated transporters, the roles of insulin and of lipid droplets, the emerging role of metabolism in microglia, mysteries about the major brain cofactor and signaling molecule NAD, as well as unsolved problems underlying brain metabolism in pathologies such as traumatic brain injury, epilepsy, and metabolic downregulation during hibernation.

A functional account of stimulation-based aerobic glycolysis and its role in interpreting BOLD signal intensity increases in neuroimaging experiments.

In aerobic glycolysis, oxygen is abundant, and yet cells metabolize glucose without using it, decreasing their ATP per glucose yield by 15-fold. During task-based stimulation, aerobic glycolysis occurs in localized brain regions, presenting a puzzle: why produce ATP inefficiently when, all else being equal, evolution should favor the efficient use of metabolic resources? The answer is that all else is not equal. We propose that a tradeoff exists between efficient ATP production and the efficiency with which ATP is spent to transmit information.

Neurovascular coupling is optimized to compensate for the increase in proton production from nonoxidative glycolysis and glycogenolysis during brain activation and maintain homeostasis of pH, pCO, and pO.

During transient brain activation cerebral blood flow (CBF) increases substantially more than cerebral metabolic rate of oxygen consumption (CMRO) resulting in blood hyperoxygenation, the basis of BOLD-fMRI contrast. Explanations for the high CBF versus CMRO slope, termed neurovascular coupling (NVC) constant, focused on maintenance of tissue oxygenation to support mitochondrial ATP production. However, paradoxically the brain has a 3-fold lower oxygen extraction fraction (OEF) than other organs with high energy requirements, like heart and muscle during exercise.