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Abstract
Glucose is the long-established, obligatory fuel for brain that fulfills many critical
functions, including ATP production, oxidative stress management, and synthesis of
neurotransmitters, neuromodulators, and structural components. Neuronal glucose oxidation
exceeds that in astrocytes, but both rates increase in direct proportion to excitatory
neurotransmission; signaling and metabolism are closely coupled at the local level.
Exact details of neuron-astrocyte glutamate-glutamine cycling remain to be established,
and the specific roles of glucose and lactate in the cellular energetics of these
processes are debated. Glycolysis is preferentially upregulated during brain activation
even though oxygen availability is sufficient (aerobic glycolysis). Three major pathways,
glycolysis, pentose phosphate shunt, and glycogen turnover, contribute to utilization
of glucose in excess of oxygen, and adrenergic regulation of aerobic glycolysis draws
attention to astrocytic metabolism, particularly glycogen turnover, which has a high
impact on the oxygen-carbohydrate mismatch. Aerobic glycolysis is proposed to be predominant
in young children and specific brain regions, but re-evaluation of data is necessary.
Shuttling of glucose- and glycogen-derived lactate from astrocytes to neurons during
activation, neurotransmission, and memory consolidation are controversial topics for
which alternative mechanisms are proposed. Nutritional therapy and vagus nerve stimulation
are translational bridges from metabolism to clinical treatment of diverse brain disorders.
[1
]Department of Neurology, University of Arkansas for Medical Sciences, Little Rock,
Arkansas; and Department of Cell Biology and Physiology, University of New Mexico,
Albuquerque, New Mexico