Cellular links between neuronal activity and energy homeostasis

Frontiers in Pharmacology

Volumn 3 MAR, Issue , 2012, Pages

  Shetty, Pavan K ^a   Galeffi, Francesca ^a   Turner, Dennis A ^a  

^a DUKE UNIVERSITY   (United States)

Author keywords

ATP; cerebral metabolism; Hippocampus; lactate; NADH; neuronal metabolism; oxygen; pyruvate

Indexed keywords

ADENOSINE; ADENOSINE TRIPHOSPHATASE (POTASSIUM SODIUM); ADENOSINE TRIPHOSPHATE; FLAVINE ADENINE NUCLEOTIDE; FLUORODEOXYGLUCOSE F 18; GLUCOSE; GLUTAMATE TRANSPORTER; GLUTAMIC ACID; GLYCOGEN; INSULIN; LEPTIN; OXYGEN; OXYGEN 15; REDUCED NICOTINAMIDE ADENINE DINUCLEOTIDE;

ARTICLE; ASTROCYTE; BASAL NEURONAL METABOLISM; BOLD SIGNAL; BRAIN BLOOD FLOW; BRAIN BLOOD VESSEL; BRAIN FUNCTION; BRAIN METABOLISM; BRAIN SLICE; CALCIUM METABOLISM; CELL METABOLISM; CELLULAR DISTRIBUTION; CEREBRAL METABOLIC UNIT; ENERGY METABOLISM; EXTRACELLULAR SPACE; FUNCTIONAL MAGNETIC RESONANCE IMAGING; GLIA CELL; GLUCOSE METABOLISM; HUMAN; METABOLIC REGULATION; NERVE CELL; NERVE CELL EXCITABILITY; NERVE CELL MEMBRANE STEADY POTENTIAL; NERVE ENDING; NERVE EXCITABILITY; NERVOUS SYSTEM PARAMETERS; NEUROIMAGING; NEURONAL ACTIVITY; NONHUMAN; OXYGEN CONSUMPTION; POSITRON EMISSION TOMOGRAPHY; POSTSYNAPTIC POTENTIAL; POTASSIUM TRANSPORT; REM SLEEP; SIGNAL TRANSDUCTION; SODIUM TRANSPORT;

EID: 84865993166     PISSN: None     EISSN: 16639812     Source Type: Journal    
DOI: 10.3389/fphar.2012.00043     Document Type: Article

References (183)

1. Abbracchio, M. P., and Burnstock, G. (1994). Purinoceptors: are there families of P2X and P2Y purinoceptors? Pharmacol. Ther. 64, 445-475.
2. Ahn, B. H., Kim, H. S., Song, S., Lee, I. H., Liu, J., Vassilopoulos, A., Deng, C. X., and Finkel, T. (2008). A role for the mitochondrial deacetylase Sirt3 in regulating energy homeostasis. Proc. Natl. Acad. Sci. U.S.A. 105, 14447-14452.
3. Amaral, A. I., Teixeira, A. P., Sonnewald, U., and Alves, P. M. (2011). Estimation of intracellular fluxes in cerebellar neurons after hypoglycemia: importance of the pyruvate recycling pathway and glutamine oxidation. J. Neurosci. Res. 89, 700-710.
4. Amiel, S. A. (1997). Hypoglycaemia in diabetes mellitus - protecting the brain. Diabetologia 40(Suppl. 2), S62-S68.
5. Anderson, C. M., and Swanson, R. A. (2000). Astrocyte glutamate transport: review of properties, regulation, and physiological functions. Glia 32, 1-14.
6. Attwell, D., Buchan, A. M., Charpak, S., Lauritzen, M., Macvicar, B. A., and Newman, E. A. (2010). Glial and neuronal control of brain blood flow. Nature 468, 232- 243.
7. Auger, C., and Attwell, D. (2000). Fast removal of synaptic glutamate by postsynaptic transporters. Neuron 28, 547-558.
8. Bachelard, H. S., Cox, D. W., and Drower, J. (1984). Sensitivity of guinea-pig hippocampal granule cell field potentials to hexoses in vitro: an effect on cell excitability? J. Physiol. 352, 91-102.
9. Bak, L. K., Schousboe, A., Sonnewald, U., and Waagepetersen, H. S. (2006). Glucose is necessary to maintain neurotransmitter homeostasis during synaptic activity in cultured glutamatergic neurons. J. Cereb. Blood Flow Metab. 26, 1285- 1297.
10. Bak, L. K., Walls, A. B., Schousboe, A., Ring, A., Sonnewald, U., and Waagepetersen, H. S. (2009). Neuronal glucose but not lactate utilization is positively correlated with NMDA-induced neurotransmission and fluctuations in cytosolic Ca2+ levels. J. Neurochem. 109(Suppl. 1), 87-93.
11. Balazs,R.,Machiyama,Y.,Hammond,B. J., Julian, T., and Richter, D. (1970). The operation of the gammaaminobutyrate bypath of the tricarboxylic acid cycle in brain tissueinvitro.Biochem. J. 116, 445- 461.
12. Barceló-Torns, M., Lewis, A. M., Gubern, A., Barneda, D., Blooryoung, D., Picatoste, F., Churchill, G. C., Claro, E., and Masgrau, R. (2011). NAADP mediates ATP-induced Ca2+ signals in astrocytes. FEBS Lett. 585, 2300- 2306.
13. Bardoni, R., Goldstein, P. A., Lee, C. J., Gu, J. G., and Macdermott, A. B. (1997). ATP P2X receptors mediate fast synaptic transmission in the dorsal horn of the rat spinal cord. J. Neurosci. 17, 5297-5304.
14. Bennett, M. R., and Ho, S. (1992). Adenosine modulation of potassium currents in preganglionic nerve terminals of avian ciliary ganglia. Neurosci. Lett. 137, 41-44.
15. Benninger, C., Kadis, J., and Prince, D. A. (1980). Extracellular calcium and potassium changes in hippocampal slices. Brain Res. 187, 165-182.
16. Bondareff, W., and Pysh, J. J. (1968). Distribution of the extracellular space during postnatal maturation of rat cerebral cortex. Anat. Rec. 160, 773-780.
17. Bourke, R. S., Kimelberg, H. K., Nelson, L. R.,Barron, K. D., Auen,E. L.,Popp, A. J., and Waldman, J. B. (1980). Biology of glial swelling in experimental brain edema. Adv. Neurol. 28, 99-109.
18. Brown, A. M., Baltan Tekkok, S., and Ransom, B. R. (2004). Energy transfer from astrocytes to axons: the role of CNS glycogen. Neurochem. Int. 45, 529-536.
19. Buchheim, K., Schuchmann, S., Siegmund, H., Gabriel, H. J., Heinemann, U., and Meierkord, H. (1999). Intrinsic optical signal measurements reveal characteristic features during different forms of spontaneous neuronal hyperactivity associated with ECS shrinkage in vitro. Eur. J. Neurosci. 11, 1877-1882.
20. Burnstock, G. (1999). Current status of purinergic signalling in the nervous system. Prog. Brain Res. 120, 3-10.
21. Butt, A. M. (2011). ATP: a ubiquitous gliotransmitter integrating neuronglial networks. Semin. Cell Dev. Biol. 22, 205-213.
22. Cataldo, A. M., and Broadwell, R. D. (1986). Cytochemical identification of cerebral glycogen and glucose-6-phosphatase activity under normal and experimental conditions. II. Choroid plexus and ependymal epithelia, endothelia and pericytes. J. Neurocytol. 15, 511-524.
23. Cesar, M., and Hamprecht, B. (1995). Immunocytochemical examination of neural rat and mouse primary cultures using monoclonal antibodies raised against pyruvate carboxylase. J. Neurochem. 64, 2312-2318.
24. Chapman, A. G., Westerberg, E., and Siesjo, B. K. (1981). The metabolism of purine and pyrimidine nucleotides in rat cortex during insulin-induced hypoglycemia and recovery. J. Neurochem. 36, 179-189.
25. Charles, A. C., Merrill, J. E., Dirksen, E. R., and Sanderson, M. J. (1991). Intercellular signaling in glial cells: calcium waves and oscillations in response to mechanical stimulation and glutamate. Neuron 6, 983-992.
26. Chatton, J.-Y., Marquet, P., and Magistretti, P. J. (2000). A quantitative analysis of l-glutamate-regulated Na+ dynamics in mouse cortical astrocytes: implications for cellular bioenergetics. Eur. J. Neurosci. 12, 3843-3853.
27. Chen, J., Zhou, Y., Mueller-Steiner, S., Chen, L. F., Kwon, H., Yi, S., Mucke, L., and Gan, L. (2005). SIRT1 protects against microglia-dependent amyloid-beta toxicity through inhibiting NF-kappaB signaling. J. Biol. Chem. 280, 40364-40374.
28. Chih, C.-P., and Roberts,Jr. E. L. (2003). Energy substrates for neurons during neural activity: a critical review of the astrocyteneuron lactate shuttle hypothesis. J. Cereb. Blood Flow Metab. 23, 1263-1281.
29. Choi, I. Y., and Gruetter, R. (2003). In vivo 13C NMR assessment of brain glycogen concentration and turnover in the awake rat. Neurochem. Int. 43, 317-322.
30. Ciricillo, S. P., Hill, M. P., Gonzalez, M. F., Smalley, S., Morton, M. T., and Sharp, F. R. (1994). Whisker stimulation metabolically activates thalamus following cortical transplantation but not following cortical ablation. Neuroscience 59, 975-992.
31. Clark, N. C., Nagano, N., Kuenzi, F. M., Jarolimek, W., Huber, I., Walter, D., Wietzorrek, G., Boyce, S., Kullmann, D. M., Striessnig, J., and Seabrook, G. R. (2003). Neurological phenotype and synaptic function in mice lacking the CaV1.3 alpha subunit of neuronal L-type voltage-dependent Ca2+ channels. Neuroscience 120, 435-442.
32. Clarke, D., and Sokoloff, L. (1999). " Circulation and energy metabolism of the brain," in Basic Neurochemistry: Molecular, Cellular, and Medical Aspects, 5th Edn, eds G. Siegel, B. Agranoff, R. W. Albers, and P. Molinoff (New York: Raven Press), 645-680.
33. Connors, B. W., Ransom, B. R., Kunis, D. M., and Gutnick, M. J. (1982). Activity-dependent K+ accumulation in the developing rat optic nerve. Science 216, 1341-1343.
34. Cook, S. P., Vulchanova, L., Hargreaves, K. M., Elde, R., and Mccleskey, E. W. (1997). Distinct ATP receptors on pain-sensing and stretch-sensing neurons. Nature 387, 505-508.
35. Cruz, N. F., and Dienel, G. A. (2002). High glycogen levels in brains of rats with minimal environmental stimuli: implications for metabolic contributions of working astrocytes. J. Cereb. Blood Flow Metab. 22, 1476-1489.
36. Danbolt, N. C. (2001). Glutamate uptake. Prog. Neurobiol. 65, 1-105.
37. Davis, K. D., Kwan, C. L., Crawley, A. P., and Mikulis, D. J. (1998). Functional MRI study of thalamic and cortical activations evoked by cutaneous heat, cold, and tactile stimuli. J. Neurophysiol. 80, 1533-1546.
38. Denton, R. M. (2009). Regulation of mitochondrial dehydrogenases by calcium ions. Biochim. Biophys. Acta 1787, 1309-1316.
39. Biase, V. D., Tuluc, P., Campiglio, M., Obermair, G. J., Heine, M., and Flucher, B. E. (2011). Surface traffic of dendritic CaV1.2 calcium channels in hippocampal neurons. J. Neurosci. 31, 13682-13694.
40. Dienel, G. A., and Cruz, N. F. (2006). Astrocyte activation in working brain:energy supplied by minor substrates. Neurochem. Int. 48, 586-595.
41. Dienel, G. A., and Hertz, L. (2001). Glucose and lactate metabolism during brain activation. J. Neurosci. Res. 66, 824-838.
42. Dietzel, I., Heinemann, U., Hofmeier, G., and Lux, H. D. (1982). Stimulusinduced changes in extracellular Na+ and Clconcentration in relation to changes in the size of the extracellular space. Exp. Brain Res. 46, 73-84.
43. Dringen, R., Wiesinger, H., and Hamprecht,B. (1993). Uptake of L-lactate by cultured rat brain neurons. Neurosci. Lett. 163, 5-7.
44. Du, F., Zhu, X.-H., Zhang, Y., Friedman, M., Zhang, N., Ugurbil, K., and Chen, W. (2008). Tightly coupled brain activity and cerebral ATP metabolic rate. Proc. Natl. Acad. Sci. U.S.A. 105, 6409-6414.
45. Duchen, M. R. (1992). Ca(2+)dependent changes in the mitochondrial energetics in single dissociated mouse sensory neurons. Biochem. J. 283(Pt 1), 41-50.
46. Elman, I., Sokoloff, L., Adler, C. M., Weisenfeld, N., and Breier,A. (1999). The effects of pharmacological doses of 2-deoxyglucose on cerebral blood flow in healthy volunteers. Brain Res. 815, 243-249.
47. Elmquist, J. K., Maratos-Flier, E., Saper, C. B., and Flier, J. S. (1998). Unraveling the central nervous system pathways underlying responses to leptin. Nat. Neurosci. 1, 445-450.
48. Fan, P., O'Regan, P. A., and Szerb, J. C. (1988). Effect of low glucose concentration on synaptic transmission in the rat hippocampal slice. Brain Res. Bull. 21, 741-747.
49. Fayuk, D., Aitken, P. G., Somjen, G. G., and Turner, D. A. (2002). Two different mechanisms underlie reversible, intrinsic optical signals in rat hippocampal slices. J. Neurophysiol. 87, 1924-1937.
50. Fields, R. D., and Stevens, B. (2000). ATP: an extracellular signaling molecule between neurons and glia. Trends Neurosci. 23, 625-633.
51. Foster, K. A., Beaver, C. J., and Turner, D. A. (2005). Interaction between tissue oxygen tension and NADH imaging during synaptic stimulation and hypoxia in rat hippocampal slices. Neuroscience 132, 645-657.
52. Fowler, J. C. (1992). Escape from inhibition of synaptic transmission during in vitro hypoxia and hypoglycemia in the hippocampus. Brain Res. 573, 169-173.
53. Fowler, J. C. (1993). Purine release and inhibition of synaptic transmission during hypoxia and hypoglycemia in rat hippocampal slices. Neurosci. Lett. 157, 83-86.
54. Fox, P. T., Mintun, M. A., Reiman, E. M., and Raichle, M. E. (1988). Enhanced detection of focal brain responses using intersubject averaging and change-distribution analysis of subtracted PET images. J. Cereb. Blood Flow Metab. 8, 642-653.
55. Furchgott, R. F., and Zawadzki, J. V. (1980). The obligatory role of endothelial cells in the relaxation of arterial smooth muscle by acetylcholine. Nature 288, 373-376.
56. Galeffi, F., Foster, K. A., Sadgrove, M. P., Beaver, C. J., and Turner, D. A. (2007). Lactate uptake contributes to the NAD(P)H biphasic response and tissue oxygen response during synaptic stimulation in area CA1 of rat hippocampal slices. J. Neurochem. 103, 2449-2461.
57. Galeffi, F., Somjen, G. G., Foster, K. A., and Turner, D. A. (2011). Simultaneous monitoring of tissue PO2 and NADH fluorescence during synaptic stimulation and spreading depression reveals a transient dissociation between oxygen utilization and mitochondrial redox state in rat hippocampal slices. J. Cereb. Blood Flow Metab. 31, 626-639.
58. Ghosh, A., Cheung, Y. Y., Mansfield, B. C., and Chou, J. Y. (2005). Brain contains a functional glucose6-phosphatase complex capable of endogenous glucose production. J. Biol. Chem. 280, 11114-11119.
59. Gibbs, M. E., Anderson, D. G., and Hertz, L. (2006). Inhibition of glycogenolysis in astrocytes interrupts memory consolidation in young chickens. Glia 54, 214-222.
60. Gibbs, M. E., Lloyd, H. G., Santa, T., and Hertz, L. (2007). Glycogen is a preferred glutamate precursor during learning in 1-day-old chick: biochemical and behavioral evidence. J. Neurosci. Res. 85, 3326-3333.
61. Gordon,G. R.,Choi,H. B.,Rungta,R. L., Ellis-Davies, G. C., and Macvicar, B. A. (2008). Brain metabolism dictates the polarity of astrocyte control over arterioles. Nature 456, 745-749.
62. Grafton, S. T., Mazziotta, J. C., Presty, S., Friston, K. J., Frackowiak, R. S., and Phelps, M. E. (1992). Functional anatomy of human procedural learning determined with regional cerebral blood flow and PET. J. Neurosci. 12, 2542-2548.
63. Greco, S. J., Hamzelou, A., Johnston, J. M., Smith, M. A., Ashford, J. W., and Tezapsidis, N. (2011). Leptin boosts cellular metabolism by activating AMPK and the sirtuins to reduce tau phosphorylation and beta-amyloid in neurons. Biochem. Biophys. Res. Commun. 414, 170-174.
64. Greco, S. J., Sarkar, S., Casadesus, G., Zhu, X., Smith, M. A., Ashford, J. W., Johnston, J. M., and Tezapsidis, N. (2009). Leptin inhibits glycogen synthase kinase-3beta to prevent tau phosphorylation in neuronal cells. Neurosci. Lett. 455, 191-194.
65. Green, E. M., Barrett, C. F., Bultynck, G., Shamah, S. M., and Dolmetsch, R. E. (2007). The tumor suppressor eIF3e mediates calcium-dependent internalization of the L-type calcium channel CaV1.2. Neuron 55, 615-632.
66. Gruetter,R.,Seaquist,E. R.,and Ugurbil, K. (2001). A mathematical model of compartmentalized neurotransmitter metabolism in the human brain. Am. J. Physiol. Endocrinol. Metab. 281, E100-E112.
67. Hakansson, M. L., Brown, H., Ghilardi, N., Skoda, R. C., and Meister, B. (1998). Leptin receptor immunoreactivity in chemically defined target neurons of the hypothalamus. J. Neurosci. 18, 559-572.
68. Hallows, W. C., Lee, S., and Denu, J. M. (2006). Sirtuins deacetylate and activate mammalian acetyl-CoA synthetases. Proc. Natl. Acad. Sci. U.S.A. 103, 10230-10235.
69. Hallows, W. C., Yu, W., Smith, B. C., Devries, M. K., Ellinger, J. J., Someya, S., Shortreed, M. R., Prolla, T., Markley, J. L., Smith, L. M., Zhao, S., Guan, K. L., and Denu, J. M. (2011). Sirt3 promotes the urea cycle and fatty acid oxidation during dietary restriction. Mol. Cell 41, 139-149.
70. Harvey, J. (2003). Novel actions of leptin in the hippocampus. Ann. Med. 35, 197-206.
71. Hell, J. W., Westenbroek, R. E., Warner, C., Ahlijanian, M. K., Prystay, W., Gilbert, M. M., Snutch, T. P., and Catterall, W. A. (1993). Identification and differential subcellular localization of the neuronal class C and class D L-type calcium channel alpha 1 subunits. J. Cell Biol. 123, 949-962.
72. Hertz, L., and Dienel, G. A. (2002). Energy metabolism in the brain. Int. Rev. Neurobiol. 51, 1-102.
73. Hertz, L., Peng, L., and Dienel, G. A. (2007). Energy metabolism in astrocytes: high rate of oxidative metabolism and spatiotemporal dependence on glycolysis/glycogenolysis. J. Cereb. Blood Flow Metab. 27, 219-249.
74. Hirschey, M. D., Shimazu, T., Capra, J. A., Pollard, K. S., and Verdin, E. (2011a). SIRT1 and SIRT3 deacetylate homologous substrates: AceCS1,2 and HMGCS1,2. Aging (Albany NY) 3, 635-642.
75. Hirschey, M. D., Shimazu, T., Huang, J. Y., Schwer, B., and Verdin, E. (2011b). SIRT3 regulates mitochondrial protein acetylation and intermediary metabolism. Cold Spring Harb. Symp. Quant. Biol. doi: 10.1101/sqb.2011.76.010850. [Epub ahead of print].
76. Hirschey ,M. D., Shimazu, T., Goetzman, E., Jing, E., Schwer, B., Lombard, D. B., Grueter, C. A., Harris, C., Biddinger, S., Ilkayeva, O. R., Stevens, R. D., Li, Y., Saha, A. K., Ruderman, N. B., Bain, J. R., Newgard, C. B., Farese, Jr. R. V., Alt, F. W., Kahn, C. R., and Verdin, E. (2010). SIRT3 regulates mitochondrial fatty-acid oxidation by reversible enzyme deacetylation. Nature 464, 121-125.
77. Hochwald, G. M., Nakamura, S., and Camins, M. B. (1981). The rat in experimental obstructive hydrocephalus. Z. Kinderchir. 34, 403-410.
78. Hoge, R. D., Atkinson, J., Gill, B., Crelier, G. R., Marrett, S., and Pike, G. B. (1999). Stimulus-dependent BOLD and perfusion dynamics in human V1. Neuroimage 9, 573-585.
79. Holmgren, C. D., Mukhtarov, M., Malkov, A. E., Popova, I. Y., Bregestovski, P., and Zilberter, Y. (2010). Energy substrate availability as a determinant of neuronal resting potential, GABA signaling and spontaneous network activity in the neonatal cortex in vitro. J. Neurochem. 112, 900-912.
80. Hu, Y., and Wilson, G. S. (1997a). Rapid changes in local extracellular rat brain glucose observed with an in vivo glucose sensor. J. Neurochem. 68, 1745-1752.
81. Hu, Y., and Wilson, G. S. (1997b). A temporary local energy pool coupled to neuronal activity: fluctuations of extracellular lactate levels in rat brain monitored with rapid-response enzymebased sensor. J. Neurochem. 69, 1484-1490.
82. Huang, J. Y., Hirschey, M. D., Shimazu, T., Ho, L., and Verdin, E. (2010). Mitochondrial sirtuins. Biochim. Biophys. Acta 1804, 1645-1651.
83. Hyder, F., Kida, I., Behar, K. L., Kennan, R. P., Maciejewski, P. K., and Rothman, D. L. (2001). Quantitative functional imaging of the brain: towards mapping neuronal activity by BOLD fMRI. NMR. Biomed. 14, 413-431.
84. Iadecola, C., and Nedergaard, M. (2007). Glial regulation of the cerebral microvasculature. Nat. Neurosci. 10, 1369-1376.
85. Ido, Y., Chang, K., and Williamson, J. R. (2004). NADH augments blood flow in physiologically activated retina and visual cortex. Proc. Natl. Acad. Sci. U.S.A. 101, 653-658.
86. Ivanov,A.,Mukhtarov,M.,Bregestovski, P., and Zilberter, Y. (2011). Lactate effectively covers energy demands during neuronal network activity in neonatal hippocampal slices. Front Neuroenergetics 3:2. doi:10.3389/fnene.2011.00002
87. Ivanov, A., and Zilberter, Y. (2011). Critical state of energy metabolism in brain slices: the principal role of oxygen delivery and energy substrates in shaping neuronal activity. Front Neuroenergetics 3:9. doi:10.3389/fnene.2011.00009
88. Izumi, Y., Ishii, K., Katsuki, H., Benz, A. M., and Zorumski, C. F. (1998). beta-Hydroxybutyrate fuels synaptic function during development. Histological and physiological evidence in rat hippocampal slices. J. Clin. Invest. 101, 1121-1132.
89. Jensen, B. S., Jessen, F., and Hoffmann, E. K. (1993). Na+,K+, Clcotransport and its regulation in Ehrlich ascites tumor cells. Ca2+/calmodulin and protein kinase C dependent pathways. J. Membr. Biol. 131, 161-178.
90. Kapogiannis, D., and Mattson, M. P. (2011). Disrupted energy metabolism and neuronal circuit dysfunction in cognitive impairment and Alzheimer's disease. Lancet Neurol. 10, 187-198.
91. Kastritsis, C. H., Salm, A. K., and Mccarthy, K. (1992). Stimulation of the P2Y purinergic receptor on type 1 astroglia results in inositol phosphate formation and calcium mobilization. J. Neurochem. 58, 1277-1284.
92. Keelan, J., Vergun, O., and Duchen, M. R. (1999). Excitotoxic mitochondrial depolarisation requires both calcium and nitric oxide in rat hippocampal neurons. J. Physiol. (Lond.) 520(Pt 3), 797-813.
93. Kim, S. H., Lu, H. F., and Alano, C. C. (2011). Neuronal Sirt3 protects against excitotoxic injury in mouse cortical neuron culture. PLoS ONE 6, e14731. doi:10.1371/journal.pone.0014731
94. Knopfel, T., Spuler, A., Grafe, P., and Gahwiler, B. H. (1990). Cytosolic calcium during glucose deprivation in hippocampal pyramidal cells of rats. Neurosci. Lett. 117, 295-299.
95. Koehler, R. C., Roman, R. J., and Harder, D. R. (2009). Astrocytes and the regulation of cerebral blood flow. Trends Neurosci. 32, 160-169.
96. Korf, J. (2006). Is brain lactate metabolized immediately after neuronal activity through the oxidative pathway? J. Cereb. Blood Flow Metab. 26, 1584-1586.
97. Kovacs, R., Schuchmann, S., Gabriel, S., Kardos, J., and Heinemann, U. (2001). Ca2+ signalling and changes of mitochondrial function during low-Mg2+-induced epileptiform activity in organotypic hippocampal slice cultures. Eur. J. Neurosci. 13, 1311-1319.
98. Lamanna, J. C., Mccracken, K. A., Patil, M., and Prohaska, O. J. (1989). Stimulus-activated changes in brain tissue temperature in the anesthetized rat. Metab. Brain Dis. 4, 225-237.
99. Lamanna, J. C., Rosenthal, M., Novack, R., Moffett, D. F., and Jobsis, F. F. (1980). Temperature coefficients for the oxidative metabolic responses to electrical stimulation in cerebral cortex. J. Neurochem. 34, 203-209.
100. Lipton, P., and Whittingham, T. S. (1979). The effect of hypoxia on evoked potentials in the in vitro hippocampus. J. Physiol. (Lond.) 287, 427-438.
101. Lipton, P., and Whittingham, T. S. (1982). Reduced ATP concentration as a basis for synaptic transmission failure during hypoxia in the in vitro guinea-pig hippocampus. J. Physiol. (Lond.) 325, 51-65.
102. Lothman, E., Lamanna, J., Cordingley, G., Rosenthal, M., and Somjen, G. (1975). Responses of electrical potential, potassium levels, and oxidative metabolic activity of the cerebral neocortex of cats. Brain Res. 88, 15-36.
103. Lupica, C. R., Proctor, W. R., and Dunwiddie, T. V. (1992). Presynaptic inhibition of excitatory synaptic transmission by adenosine in rat hippocampus: analysis of unitary EPSP variance measured by whole-cell recording. J. Neurosci. 12, 3753-3764.
104. Magistretti, P. J. (2006). Neuron-glia metabolic coupling and plasticity. J. Exp. Biol. 209, 2304-2311.
105. Magistretti, P. J., Cardinaux, J. R., and Martin, J. L. (1998). VIP and PACAP in the CNS: regulators of glial energy metabolism and modulators of glutamatergic signaling. Ann. N. Y. Acad. Sci. 865, 213-225.
106. Magistretti, P. J., and Pellerin, L. (1999). Cellular mechanisms of brain energy metabolism and their relevance to functional brain imaging. Philos. Trans. R. Soc. Lond. B Biol. Sci. 354, 1155-1163.
107. Malarkey, E. B., and Parpura, V. (2008). Mechanisms of glutamate release from astrocytes. Neurochem. Int. 52, 142-154.
108. Mckenna, M. C., Sonnewald, U., Huang, X., Stevenson, J., and Zielke, H. R. (1996a). Exogenous glutamate concentration regulates the metabolic fate of glutamate in astrocytes. J. Neurochem. 66, 386-393.
109. Mckenna, M. C., Tildon, J. T., Stevenson, J. H., and Huang, X. (1996b). New insights into the compartmentation of glutamate and glutamine in cultured rat brain astrocytes. Dev. Neurosci. 18, 380-390.
110. Michan, S., and Sinclair, D. (2007). Sirtuins in mammals: insights into their biological function. Biochem. J. 404, 1-13.
111. Mogul, D. J., Adams, M. E., and Fox, A. P. (1993). Differential activation of adenosine receptors decreases Ntype but potentiates P-type Ca2+ current in hippocampal CA3 neurons. Neuron 10, 327-334.
112. Moreadith, R. W., and Lehninger, A. L. (1984). The pathways of glutamate and glutamine oxidation by tumor cell mitochondria. Role of mitochondrial NAD(P)+dependent malic enzyme. J. Biol. Chem. 259, 6215-6221.
113. Mukhtarov, M., Ivanov, A., Zilberter, Y., and Bregestovski, P. (2011). Inhibition of spontaneous network activity in neonatal hippocampal slices by energy substrates is not correlated with intracellular acidification. J. Neurochem. 116, 316-321.
114. Naito, S., and Ueda, T. (1983). Adenosine triphosphate-dependent uptake of glutamate into protein Iassociated synaptic vesicles. J. Biol. Chem. 258, 696-699.
115. Nelson, M. T., and Quayle, J. M. (1995). Physiological roles and properties of potassium channels in arterial smooth muscle. Am. J. Physiol. 268, C799-C822.
116. Norenberg, M. D., and Hernandez, A.M. (1979). Fine structural localization of glutamine synthetase in astrocytes of rat brain. Brain Res. 161, 303-310.
117. Obermair, G. J., Szabo, Z., Bourinet, E., and Flucher, B. E. (2004). Differential targeting of the Ltype Ca2+ channel alpha 1C (CaV1.2) to synaptic and extrasynaptic compartments in hippocampal neurons. Eur. J. Neurosci. 19, 2109-2122.
118. Offenhauser, N., Thomsen, K., Caesar, K., and Lauritzen, M. (2005). Activity-induced tissue oxygenation changes in rat cerebellar cortex: interplay of postsynaptic activation and blood flow. J. Physiol. 565, 279-294.
119. O'Neill, W. C. (1999). Physiological significance of volume-regulatory transporters. Am. J. Physiol. 276, C995-C1011.
120. Ozkan, E. D., and Ueda, T. (1998). Glutamate transport and storage in synaptic vesicles. Jpn. J. Pharmacol. 77, 1-10.
121. Pangrsic, T., Potokar, M., Stenovec, M., Kreft, M., Fabbretti, E., Nistri, A., Pryazhnikov, E., Khiroug, L., Giniatullin, R., and Zorec, R. (2007). Exocytotic release of ATP from cultured astrocytes. J. Biol. Chem. 282, 28749-28758.
122. Pankratov, Y., Lalo, U., Verkhratsky, A., and North, R. (2006). Vesicular release of ATP at central synapses. Pflügers Arch. 452, 589-597.
123. Parpura, V., Basarsky, T. A., Liu, F., Jeftinija, K., Jeftinija, S., and Haydon, P. G. (1994). Glutamate-mediated astrocyte-neuron signalling. Nature 369, 744-747.
124. Pascual, O., Casper, K. B., Kubera, C., Zhang, J., Revilla-Sanchez, R., Sul, J.Y., Takano, H., Moss, S. J., Mccarthy, K., and Haydon, P. G. (2005). Astrocytic purinergic signaling coordinates synaptic networks. Science 310, 113-116.
125. Paulson, O. B., Hasselbalch, S. G., Rostrup, E., Knudsen, G. M., and Pelligrino, D. (2009). Cerebral blood flow response to functional activation. J. Cereb. Blood Flow Metab. 30, 2-14.
126. Pellerin, L., Bouzier-Sore, A. K., Aubert, A., Serres, S., Merle, M., Costalat, R., and Magistretti,P. J. (2007).Activitydependent regulation of energy metabolism by astrocytes: an update. Glia 55, 1251-1262.
127. Pellerin, L., and Magistretti, P. J. (1994). Glutamate uptake into astrocytes stimulates aerobic glycolysis: a mechanism coupling neuronal activity to glucose utilization. Proc. Natl. Acad. Sci. U.S.A. 91, 10625-10629.
128. Pellerin, L., and Magistretti, P. J. (1996). Excitatory amino acids stimulate aerobic glycolysis in astrocytes via an activation of the Na+/K+ ATPase. Dev. Neurosci. 18, 336-342.
129. Pellerin, L., and Magistretti, P. J. (1997). Glutamate uptake stimulates Na+, K+ -ATPase activity in astrocytes via activation of a distinct subunit highly sensitive to ouabain. J. Neurochem. 69, 2132-2137.
130. Phelps, M. E., and Mazziotta, J. C. (1985). Positron emission tomography: human brain function and biochemistry. Science 228, 799-809.
131. Phillis, J. W., and Wu, P. H. (1981). The role of adenosine and its nucleotides in central synaptic transmission. Prog. Neurobiol. 16, 187-239.
132. Puchowicz, M. A., Xu, K., Sun, X., Ivy, A., Emancipator, D., and Lamanna, J. C. (2007). Diet-induced ketosis increases capillary density without altered blood flow in rat brain. Am. J. Physiol. Endocrinol. Metab. 292, E1607-E1615.
133. Qu, H., Eloqayli, H., Unsgard, G., and Sonnewald, U. (2001). Glutamate decreases pyruvate carboxylase activity and spares glucose as energy substrate in cultured cerebellar astrocytes. J. Neurosci. Res. 66, 1127-1132.
134. Ransom, B. R., Yamate, C. L., and Connors, B. W. (1985). Activitydependent shrinkage of extracellular space in rat optic nerve: a developmental study. J. Neurosci. 5,532-535.
135. Rheims, S., Holmgren, C. D., Chazal, G., Mulder, J., Harkany, T., Zilberter, T., and Zilberter, Y. (2009). GABA action in immature neocortical neurons directly depends on the availability of ketone bodies. J. Neurochem. 110, 1330-1338.
136. Rosenthal, M., and Jobsis, F. F. (1971). Intracellular redox changes in functioning cerebral cortex. II. Effects of direct cortical stimulation. J. Neurophysiol. 34, 750-762.
137. Rothman, D. L., Behar, K. L., Hyder, F., and Shulman, R. G. (2003). In vivo NMR studies of the glutamate neurotransmitter flux and neuroenergetics: implications for brain function. Annu. Rev. Physiol. 65, 401-427.
138. Schlick, B., Flucher, B. E., and Obermair, G. J. (2010). Voltage-activated calcium channel expression profiles in mouse brain and cultured hippocampal neurons. Neuroscience 167, 786-798.
139. Scholz, K. P., and Miller, R. J. (1991). Analysis of adenosine actions on Ca2+ currents and synaptic transmission in cultured rat hippocampal pyramidal neurones. J. Physiol. 435, 373-393.
140. Schuchmann, S., Kovacs, R., Kann, O., Heinemann, U., and Buchheim, K. (2001). Monitoring NAD(P)H autofluorescence to assess mitochondrial metabolic functions in rat hippocampal-entorhinal cortex slices. Brain Res. Brain Res. Protoc. 7, 267-276.
141. Sebastiao, A. M., and Ribeiro, J. A. (1996). Adenosine A2 receptormediated excitatory actions on the nervous system. Prog. Neurobiol. 48, 167-189.
142. Shank, R. P., Bennett, G. S., Freytag, S. O., and Campbell, G. L. (1985). Pyruvate carboxylase: an astrocytespecific enzyme implicated in the replenishment of amino acid neurotransmitter pools. Brain Res. 329, 364-367.
143. Shanley, L. J., Irving, A. J., and Harvey, J. (2001). Leptin enhances NMDA receptor function and modulates hippocampal synaptic plasticity. J. Neurosci. 21, RC186.
144. Shetty, P. K., Galeffi, F., and Turner, D. A. (2011). Age-induced alterations in hippocampal function and metabolism. Aging Dis. 2, 196-218.
145. Shetty, P. K., Sadgrove, M. P., Galeffi, F., and Turner, D. A. (2012). Pyruvate incubation enhances glycogen stores and sustains neuronal function during subsequent glucose deprivation. Neurobiol. Dis. 45, 177-187.
146. Shimazu, T., Hirschey, M. D., Hua, L., Dittenhafer-Reed, K. E., Schwer, B., Lombard, D. B., Li, Y., Bunkenborg, J., Alt, F. W., Denu, J. M., Jacobson, M. P., and Verdin, E. (2010). SIRT3 deacetylates mitochondrial 3-hydroxy-3-methylglutaryl CoA synthase 2 and regulates ketone body production. Cell Metab. 12, 654-661.
147. Shulman,R. G.,Hyder,F.,and Rothman, D. L. (2009). Baseline brain energy supports the state of consciousness. Proc. Natl. Acad. Sci. U.S.A. 106, 11096-11101.
148. Shulman, R. G., Rothman, D. L., Behar, K. L., and Hyder, F. (2004). Energetic basis of brain activity: implications for neuroimaging. Trends Neurosci. 27, 489-495.
149. Shuttleworth, C. W., Brennan, A. M., and Connor, J. A. (2003). NAD(P)H fluorescence imaging of postsynaptic neuronal activation in murine hippocampal slices. J. Neurosci. 23, 3196-3208.
150. Sibson, N. R., Mason, G. F., Shen, J., Cline, G. W., Herskovits, A. Z., Wall, J. E., Behar, K. L., Rothman, D. L., and Shulman, R. G. (2001). In vivo (13)C NMR measurement of neurotransmitter glutamate cycling, anaplerosis and TCA cycle flux in rat brain during. J. Neurochem. 76, 975-989.
151. Sickmann, H. M., Walls, A. B., Schousboe, A., Bouman, S. D., and Waagepetersen, H. S. (2009). Functional significance of brain glycogen in sustaining glutamatergic neurotransmission. J. Neurochem. 109(Suppl. 1), 80-86.
152. Simao, F., Matte, A., Matte, C., Soares, F. M., Wyse, A. T., Netto, C. A., and Salbego, C. G. (2011). Resveratrol prevents oxidative stress and inhibition of Na(+)K(+)-ATPase activity induced by transient global cerebral ischemia in rats. J. Nutr. Biochem. 22, 921-928.
153. Skou, J. C., and Esmann, M. (1992). The Na, K-ATPase. J. Bioenerg. Biomembr. 24, 249-261.
154. Smith, A. J., Blumenfeld, H., Behar, K. L., Rothman, D. L., Shulman, R. G., and Hyder, F. (2002). Cerebral energetics and spiking frequency: the neurophysiological basis of fMRI. Proc. Natl. Acad. Sci. U.S.A. 99, 10765-10770.
155. Sobey, C. G., Heistad, D. D., and Faraci, F. M. (1997). Mechanisms of bradykinin-induced cerebral vasodilatation in rats. Evidence that reactive oxygen species activate K+ channels. Stroke 28, 2290-2294; discussion 2295.
156. Sokoloff, L. (1999). Energetics of functional activation in neural tissues. Neurochem. Res. 24, 321-329.
157. Someya, S., Yu, W., Hallows, W. C., Xu, J., Vann, J. M., Leeuwenburgh, C., Tanokura, M., Denu, J. M., and Prolla, T. A. (2010). Sirt3 mediates reduction of oxidative damage and prevention of age-related hearing loss under caloric restriction. Cell 143, 802-812.
158. Somjen, G. G. (2002). Ion regulation in the brain: implications for pathophysiology. Neuroscientist 8, 254-267.
159. Su, G., Haworth, R. A., Dempsey, R. J., and Sun, D. (2000). Regulation of Na(+)-K(+)-Cl(-) cotransporter in primary astrocytes by dibutyryl cAMP and high [K(+)](o). Am. J. Physiol. Cell Physiol. 279, C1710- C1721.
160. Suh, S. W., Hamby, A. M., and Swanson, R. A. (2007). Hypoglycemia, brain energetics, and hypoglycemic neuronal death. Glia 55, 1280-1286.
161. Sukstanskii, A. L., and Yablonskiy, D. A. (2006). Theoretical model of temperature regulation in the brain during changes in functional activity. Proc. Natl. Acad. Sci. U.S.A. 103, 12144-12149.
162. Sundaresan, N. R., Samant, S. A., Pillai, V. B., Rajamohan, S. B., and Gupta, M. P. (2008). SIRT3 is a stressresponsive deacetylase in cardiomyocytes that protects cells from stressmediated cell death by deacetylation of Ku70. Mol. Cell. Biol. 28, 6384-6401.
163. Suzuki, A., Stern, S. A., Bozdagi, O., Huntley, G. W., Walker, R. H., Magistretti, P. J., and Alberini, C. M. (2011). Astrocyte-neuron lactate transport is required for longterm memory formation. Cell 144, 810-823.
164. Thompson, J. K., Peterson, M. R., and Freeman, R. D. (2003). Singleneuron activity and tissue oxygenation in the cerebral cortex. Science 299, 1070-1072.
165. Trubel, H. K. F., Sacolick, L. I., and Hyder, F. (2005). Regional temperature changes in the brain during somatosensory stimulation. J. Cereb. Blood Flow Metab. 26, 68-78.
166. Turner, D. A., Foster, K. A., Galeffi, F., and Somjen, G. G. (2007). Differences in O2 availability resolve the apparent discrepancies in metabolic intrinsic optical signals in vivo and in vitro. Trends Neurosci. 30, 390-398.
167. Berg, C. J. V. D. , and Garfinkel, D. (1971). A stimulation study of brain compartments. Metabolism of glutamate and related substances in mouse brain. Biochem. J. 123, 211-218.
168. Berg, C. J. V. D., Krzalic, L., Mela, P., and Waelsch, H. (1969). Compartmentation of glutamate metabolism in brain. Evidence for the existence of two different tricarboxylic acid cycles in brain. Biochem. J. 113, 281-290.
169. Harreveld, A. V., Khattab, F. I., and Steiner, J. (1969). Extracellular space in the central nervous system of the leech, Mooreobdella fervida. J. Neurobiol. 1, 23-40.
170. Vilchez, D., Ros, S., Cifuentes, D., Pujadas, L., Valles, J., Garcia-Fojeda, B., Criado-Garcia, O., FernandezSanchez, E., Medrano-Fernandez, I., Dominguez, J., Garcia-Rocha, M., Soriano, E.,Cordoba, S. R. D., and Guinovart, J. J. (2007). Mechanism suppressing glycogen synthesis in neurons and its demise in progressive myoclonus epilepsy. Nat. Neurosci. 10, 1407-1413.
171. Voutsinos-Porche, B., Bonvento, G., Tanaka, K., Steiner, P., Welker, E., Chatton, J. Y., Magistretti, P. J., and Pellerin, L. (2003). Glial glutamate transporters mediate a functional metabolic crosstalk between neurons and astrocytes in the mouse developing cortex. Neuron 37, 275-286.
172. Walz, W., and Hertz, L. (1982). Ouabain-sensitive and ouabainresistant net uptake of potassium into astrocytes and neurons in primary cultures. J. Neurochem. 39, 70-77.
173. Westergaard, N., Sonnewald, U., and Schousboe, A. (1995). Metabolic trafficking between neurons and astrocytes: the glutamate/glutamine cycle revisited. Dev. Neurosci. 17, 203-211.
174. White, T. D., and Macdonald, W. F. (1990). Neural release of ATP and adenosinea. Ann. N. Y. Acad. Sci. 603, 287-298.
175. William, V. D. K. (2003). Loading and recycling of synaptic vesicles in the Torpedo electric organ and the vertebrate neuromuscular junction. Prog. Neurobiol. 71, 269-303.
176. Wyss, M. T., Jolivet, R., Buck, A., Magistretti, P. J., and Weber, B. (2011). In vivo evidence for lactate as a neuronal energy source. J. Neurosci. 31, 7477-7485.
177. Yablonskiy, D. A., Ackerman, J. J., and Raichle, M. E. (2000). Coupling between changes in human brain temperature and oxidative metabolism during prolonged visual stimulation. Proc. Natl. Acad. Sci. U.S.A. 97, 7603-7608.
178. Yu, A. C., Drejer, J., Hertz, L., and Schousboe, A. (1983). Pyruvate carboxylase activity in primary cultures of astrocytes and neurons. J. Neurochem. 41, 1484-1487.
179. Yu, J., and Auwerx, J. (2009). The role of sirtuins in the control of metabolic homeostasis. Ann. N. Y. Acad. Sci. 1173(Suppl. 1), E10-E19.
180. Zhang, D., Liu, Y., and Chen, D. (2011). SIRT-ain relief from ageinducing stress. Aging (Albany NY) 3, 158-161.
181. Zhu, P. J., and Krnjevic, K. (1993). Adenosine release is a major cause of failure of synaptic transmission during hypoglycemia in rat hippocampal slices. Neurosci. Lett. 155, 128-131.
182. Zielke, H. R., Zielke, C. L., Baab, P. J., and Tildon, J. T. (2007). Effect of fluorocitrate on cerebral oxidation of lactate and glucose in freely moving rats. J. Neurochem. 101, 9-16.
183. Zilberter, Y., Zilberter, T., and Bregestovski, P. (2010). Neuronal activity in vitro and the in vivo reality: the role of energy homeostasis. Trends Pharmacol. Sci. 31, 394-401.