The focus of this application is on brain """"""""aerobic glycosis"""""""", a term applied to the disproportionately greater increase in glucose than oxygen utilization in working brain. The general hypothesis to be tested is that glucose taken up in excess of oxygen is used to restore metabolic pools depleted at the onset of stimulation, rather than to generate lactate. Dr. Dienel proposes to develop a rat model of aerobic glycosis using generalized sensory stimulation, then assay changes in brain levels of major metabolites and flux of radiolabelled glucose into major pathways, some specific to neurons (GABA) or glia (glycogen and glutamine), using biochemical, autoradiographic, and microdialysis techniques. To determine the cellular basis of metabolism during aerobic glycosis, Dr. Dienel will use radiolabelled """"""""glial reporter molecules"""""""" (butyrate, acetate) and autoradiography to examine glial contributions.

National Institute of Health (NIH)
National Institute of Neurological Disorders and Stroke (NINDS)
Research Project (R01)
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Special Emphasis Panel (ZRG1-MDCN-2 (01))
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Sato, Sheryl M
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University of Arkansas for Medical Sciences
Schools of Medicine
Little Rock
United States
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Dienel, Gerald A; Cruz, Nancy F (2015) Contributions of glycogen to astrocytic energetics during brain activation. Metab Brain Dis 30:281-98
Ball, Kelly K; Cruz, Nancy F; Mrak, Robert E et al. (2010) Trafficking of glucose, lactate, and amyloid-beta from the inferior colliculus through perivascular routes. J Cereb Blood Flow Metab 30:162-76
Gandhi, Gautam K; Ball, Kelly K; Cruz, Nancy F et al. (2010) Hyperglycaemia and diabetes impair gap junctional communication among astrocytes. ASN Neuro 2:e00030
Gandhi, Gautam K; Cruz, Nancy F; Ball, Kelly K et al. (2009) Astrocytes are poised for lactate trafficking and release from activated brain and for supply of glucose to neurons. J Neurochem 111:522-36
Gandhi, Gautam K; Cruz, Nancy F; Ball, Kelly K et al. (2009) Selective astrocytic gap junctional trafficking of molecules involved in the glycolytic pathway: impact on cellular brain imaging. J Neurochem 110:857-69
Dienel, Gerald A; Cruz, Nancy F (2009) Exchange-mediated dilution of brain lactate specific activity: implications for the origin of glutamate dilution and the contributions of glutamine dilution and other pathways. J Neurochem 109 Suppl 1:30-7
Dienel, Gerald A; Cruz, Nancy F (2008) Imaging brain activation: simple pictures of complex biology. Ann N Y Acad Sci 1147:139-70
Dienel, Gerald A; Ball, Kelly K; Cruz, Nancy F (2007) A glycogen phosphorylase inhibitor selectively enhances local rates of glucose utilization in brain during sensory stimulation of conscious rats: implications for glycogen turnover. J Neurochem 102:466-78
Ball, Kelly K; Gandhi, Gautam K; Thrash, Jarrod et al. (2007) Astrocytic connexin distributions and rapid, extensive dye transfer via gap junctions in the inferior colliculus: implications for [(14)C]glucose metabolite trafficking. J Neurosci Res 85:3267-83
Cruz, Nancy F; Ball, Kelly K; Dienel, Gerald A (2007) Functional imaging of focal brain activation in conscious rats: impact of [(14)C]glucose metabolite spreading and release. J Neurosci Res 85:3254-66

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