Effects of hypoglycaemia on neuronal metabolism in the adult brain: Role of alternative substrates to glucose

Journal of Inherited Metabolic Disease

Volumn 36, Issue 4, 2013, Pages 621-634

  Amaral, Ana I ^a  

^a UNIVERSITY OF CAMBRIDGE   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

ADENOSINE TRIPHOSPHATE; ASPARTIC ACID; GLUCOSE; GLUTAMIC ACID; GLUTAMINE; GLYCOGEN; KETONE BODY; PYRUVIC ACID;

ANALYTIC METHOD; ARTICLE; BIOENERGY; BRAIN METABOLISM; CELL METABOLISM; ENZYME METABOLISM; GLUCOSE METABOLISM; HUMAN; HYPOGLYCEMIA; IN VITRO STUDY; IN VIVO STUDY; METABOLIC FLUX ANALYSIS; NERVE CELL CULTURE; NERVE FUNCTION; NONHUMAN; PROTEIN DEPLETION; SIGNAL TRANSDUCTION;

BRAIN; ENERGY METABOLISM; GLUCOSE; HUMANS; HYPOGLYCEMIA; NEURONS; PYRUVIC ACID;

EID: 84880193432     PISSN: 01418955     EISSN: 15732665     Source Type: Journal    
DOI: 10.1007/s10545-012-9553-3     Document Type: Article

References (143)

1. Alves PM, Nunes R, Zhang C et al (2000) Metabolism of 3-(13)C-malate in primary cultures of mouse astrocytes. Dev Neurosci 22(5-6):456-462
2. Amaral AI, Teixeira AP, Martens S, Bernal V, Sousa MF, Alves PM (2010) Metabolic alterations induced by ischemia in primary cultures of astrocytes: merging 13C NMR spectroscopy and metabolic flux analysis. J Neurochem 113(3):735-748
3. Amaral AI, Teixeira AP, Hakonsen BI, Sonnewald U, Alves PM (2011a) A comprehensive metabolic profile of cultured astrocytes using isotopic transient metabolic flux analysis and C-labeled glucose. Front Neuroenerg 3:5
4. Amaral AI, Teixeira AP, Sonnewald U, Alves PM (2011b) Estimation of intracellular fluxes in cerebellar neurons after hypoglycemia: importance of the pyruvate recycling pathway and glutamine oxidation. J Neurosci Res 89(5):700-710
5. Arakawa T, Goto T, Okada Y (1991) Effect of ketone body (D-3-hydroxybutyrate) on neural activity and energy metabolism in hippocampal slices of the adult guinea pig. Neurosci Lett 130(1):53-56
6. Attwell D, Laughlin SB (2001) An energy budget for signaling in the grey matter of the brain. J Cereb Blood Flow Metab 21(10):1133-1145
7. Auer RN (2004) Hypoglycemic brain damage. Metab Brain Dis 19(3-4):169-175
8. Auer RN, Olsson Y, Siesjo BK (1984) Hypoglycemic brain injury in the rat. Correlation of density of brain damage with the EEG isoelectric time: a quantitative study. Diabetes 33(11):1090-1098
9. Bak LK, Schousboe A, Sonnewald U, Waagepetersen HS (2006a) Glucose is necessary to maintain neurotransmitter homeostasis during synaptic activity in cultured glutamatergic neurons. J Cereb Blood Flow Metab
10. Bak LK, Schousboe A, Waagepetersen HS (2006b) The glutamate/GABA- glutamine cycle: aspects of transport, neurotransmitter homeostasis and ammonia transfer. J Neurochem 98(3):641-653
11. Bakken IJ, White LR, Aasly J, Unsgard G, Sonnewald U (1997) Lactate formation from [U-13C]aspartate in cultured astrocytes: compartmentation of pyruvate metabolism. Neurosci Lett 237(2-3):117-120
12. Barros LF, Bittner CX, Loaiza A, Porras OH (2007) A quantitative overview of glucose dynamics in the gliovascular unit. Glia 55(12):1222-1237
13. Behar KL, den Hollander JA, Petroff OA, Hetherington HP, Prichard JW, Shulman RG (1985) Effect of hypoglycemic encephalopathy upon amino acids, high-energy phosphates, and pHi in the rat brain in vivo: detection by sequential 1 H and 31P NMR spectroscopy. J Neurochem 44(4):1045-1055
14. Bernal V, Carinhas N, Yokomizo AY, Carrondo MJ, Alves PM (2009) Cell density effect in the baculovirus-insect cells system: a quantitative analysis of energetic metabolism. Biotechnol Bioeng 104(1):162-180
15. Bonarius HPJ, Schmid G, Tramper J (1997) Flux analysis of underdetermined metabolic networks: the quest for the missing constraints. Trends Biotechnol 15(8):308-314
16. Bonvento G, Herard AS, Voutsinos-Porche B (2005) The astrocyte-neuron lactate shuttle: a debated but still valuable hypothesis for brain imaging. J Cereb Blood Flow Metab 25(10):1394-1399
17. Brooks KJ, Clark JB, Bates TE (1998) 3-Hydroxybutyrate aids the recovery of the energy state from aglycaemic hypoxia of adult but not neonatal rat brain slices. J Neurochem 70(5):1986-1990
18. Brown AM, Ransom BR (2007) Astrocyte glycogen and brain energy metabolism. Glia 55(12):1263-1271
19. Brown AM, Wender R, Ransom BR (2001) Metabolic substrates other than glucose support axon function in central white matter. J Neurosci Res 66(5):839-843
20. Brown AM, Baltan Tekkok S, Ransom BR (2004) Energy transfer from astrocytes to axons: the role of CNS glycogen. Neurochem Int 45(4):529-536
21. Butcher SP, Hagberg H, Sandberg M, Hamberger A (1987) Extracellular purine catabolite and amino acid levels in the rat striatum during severe hypoglycemia: Effects of 2-amino-5-phosphonovalerate. Neurochem Int 11(1):95-99
22. Calabresi P, Centonze D, Pisani A, Bernardi G (1997a) Endogenous adenosine mediates the presynaptic inhibition induced by aglycemia at corticostriatal synapses. J Neurosci 17(12):4509-4516
23. Calabresi P, Centonze D, Pisani A, Bernardi G (1997b) A possible mechanism for the aglycemia-induced depression of glutamatergic excitation in the striatum. J Cereb Blood Flow Metab 17(10):1121-1126
24. Canada SE, Weaver SA, Sharpe SN, Pederson BA (2011) Brain glycogen supercompensation in the mouse after recovery from insulin-induced hypoglycemia. J Neurosci Res 89(4):585-591
25. Cataldo A, Broadwell R (1986) Cytochemical identification of cerebral glycogen and glucose-6-phosphatase activity under normal and experimental conditions. I. Neurons and Glia. J Elect Micro Tech 3:413-437
26. Cerdan S, Kunnecke B, Seelig J (1990) Cerebral metabolism of [1,2-13C2]acetate as detected by in vivo and in vitro 13C NMR. J Biol Chem 265(22):12916-12926
27. Cerdan S, Rodrigues TB, Sierra A et al (2006) The redox switch/redox coupling hypothesis. Neurochem Int 48(6-7):523-530
28. Chapa F, Cruz F, Garcia-Martin ML, Garcia-Espinosa MA, Cerdan S (2000) Metabolism of (1-(13)C) glucose and (2-(13)C, 2-(2)H(3)) acetate in the neuronal and glial compartments of the adult rat brain as detected by [(13)C, (2)H] NMR spectroscopy. Neurochem Int 37(2-3):217-228
29. Choi IY, Lee SP, Kim SG, Gruetter R (2001) In vivo measurements of brain glucose transport using the reversible Michaelis-Menten model and simultaneous measurements of cerebral blood flow changes during hypoglycemia. J Cereb Blood Flow Metab 21(6):653-663
30. Choi IY, Seaquist ER, Gruetter R (2003) Effect of hypoglycemia on brain glycogen metabolism in vivo. J Neurosci Res 72(1):25-32
31. Clarke DD, Sokoloff L (1999) Circulation and Energy Metabolism. in G. J. Siegel, B. W. Agranoff, R. W. Albers, S. K. Fisher and M. D. Uhler (eds) Basic Neurochemistry: Molecular, Cellular and Medical Aspects: Lippincott Williams and Wilkins, 638-669
32. Criego AB, Tkac I, Kumar A, Thomas W, Gruetter R, Seaquist ER (2005) Brain glucose concentrations in patients with type 1 diabetes and hypoglycemia unawareness. J Neurosci Res 79(1-2):42-47
33. Cruz NF, Dienel GA (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(12):1476-1489
34. Cruz F, Scott SR, Barroso I, Santisteban P, Cerdan S (1998) Ontogeny and cellular localization of the pyruvate recycling system in rat brain. J Neurochem 70(6):2613-2619
35. Cryer PE (2005) Mechanisms of hypoglycemia-associated autonomic failure and its component syndromes in diabetes. Diabetes 54(12):3592-3601
36. De Vivo DC, Trifiletti RR, Jacobson RI, Ronen GM, Behmand RA, Harik SI (1991) Defective glucose transport across the blood-brain barrier as a cause of persistent hypoglycorrhachia, seizures, and developmental delay. N Engl J Med 325(10):703-709
37. Dienel GA, Cruz NF (2004) Nutrition during brain activation: does cell-to-cell lactate shuttling contribute significantly to sweet and sour food for thought? Neurochem Int 45(2-3):321-351
38. Dienel GA, Cruz NF (2008) Imaging brain activation: simple pictures of complex biology. Ann N Y Acad Sci 1147:139-170
39. Dienel GA, Ball KK, Cruz NF (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(2):466-478
40. Dringen R, Gebhardt R, Hamprecht B (1993) Glycogen in astrocytes: possible function as lactate supply for neighboring cells. Brain Res 623(2):208-214
41. Dringen R, Hoepken HH, Minich T, Ruedig C (2007) Pentose Phospahte Pathway and NADPH Metabolism. in G. Dienel and G. Gibson (eds) Brain Energetics. Integration of Molecular and Cellular Processes: Springer, 41-62
42. Duarte JMN, Lanz B, Gruetter R (2011) Compartmentalized cerebral metabolism of [1,6-13C]glucose determined by in vivo 13C NMR spectroscopy at 14.1 T. Frontiers in Neuroenergetics 3(3)
43. Edmond J, Robbins RA, Bergstrom JD, Cole RA, de Vellis J (1987) Capacity for substrate utilization in oxidative metabolism by neurons, astrocytes, and oligodendrocytes from developing brain in primary culture. J Neurosci Res 18(4):551-561
44. Evans ML, Matyka K, Lomas J et al (1998) Reduced counterregulation during hypoglycemia with raised circulating nonglucose lipid substrates: evidence for regional differences in metabolic capacity in the human brain? J Clin Endocrinol Metab 83(8):2952-2959
45. Fowler JC (1993) Glucose deprivation results in a lactate preventable increase in adenosine and depression of synaptic transmission in rat hippocampal slices. J Neurochem 60(2):572-576
46. Genabai NK, Vavaiya KV, Briski KP (2009) Adaptation of glucokinase gene expression in the rat dorsal vagal complex in a model for recurrent intermediate insulin-induced hypoglycemia: impact of gender. J Mol Neurosci 37(1):80-85
47. Gruetter R (2003) Glycogen: the forgotten cerebral energy store. J Neurosci Res 74(2):179-183
48. Gruetter R, Ugurbil K, Seaquist ER (1998) Steady-state cerebral glucose concentrations and transport in the human brain. J Neurochem 70(1):397-408
49. Gruetter R, Seaquist ER, Ugurbil K (2001) A mathematical model of compartmentalized neurotransmitter metabolism in the human brain. Am J Physiol Endocrinol Metab 281(1):E100-E112
50. Haberg A, Qu H, Bakken IJ et al (1998) In vitro and ex vivo 13C-NMR spectroscopy studies of pyruvate recycling in brain. Dev Neurosci 20(4-5):389-398
51. Haces ML, Hernandez-Fonseca K, Medina-Campos ON, Montiel T, Pedraza-Chaverri J, Massieu L (2008) Antioxidant capacity contributes to protection of ketone bodies against oxidative damage induced during hypoglycemic conditions. Exp Neurol 211(1):85-96
52. Harris RJ, Wieloch T, Symon L, Siesjo BK (1984) Cerebral extracellular calcium activity in severe hypoglycemia: relation to extracellular potassium and energy state. J Cereb Blood Flow Metab 4(2):187-193
53. Hassel B, Sonnewald U (1995) Glial formation of pyruvate and lactate from TCA cycle intermediates: implications for the inactivation of transmitter amino acids? J Neurochem 65(5):2227-2234
54. Haywood SC, Bree AJ, Puente EC, Daphna-Iken D, Fisher SJ (2009) Central but not systemic lipid infusion augments the counterregulatory response to hypoglycemia. Am J Physiol Endocrinol Metab 297(1):E50-E56
55. Henry PG, Lebon V, Vaufrey F, Brouillet E, Hantraye P, Bloch G (2002) Decreased TCA cycle rate in the rat brain after acute 3-NP treatment measured by in vivo 1 H-[13C] NMR spectroscopy. J Neurochem 82(4):857-866
56. Hernandez MJ, Vannucci RC, Salcedo A, Brennan RW (1980) Cerebral blood flow and metabolism during hypoglycemia in newborn dogs. J Neurochem 35(3):622-628
57. Hertz L, Peng L, Dienel GA (2007) Energy metabolism in astrocytes: high rate of oxidative metabolism and spatiotemporal dependence on glycolysis/glycogenolysis. J Cereb Blood Flow Metab 27(2):219-249
58. Herzog RI, Chan O, Yu S, Dziura J, McNay EC, Sherwin RS (2008) Effect of acute and recurrent hypoglycemia on changes in brain glycogen concentration. Endocrinology 149(4):1499-1504
59. Ikemoto A, Bole DG, Ueda T (2003) Glycolysis and glutamate accumulation into synaptic vesicles. Role of glyceraldehyde phosphate dehydrogenase and 3-phosphoglycerate kinase. J Biol Chem 278(8):5929-5940
60. Jiang L, Herzog RI, Mason GF (2009) Recurrent antecedent hypoglycemia alters neuronal oxidative metabolism in vivo. Diabetes 58(6):1266-1274
61. Kim YH, Kim EY, Gwag BJ, Sohn S, Koh JY (1999) Zinc-induced cortical neuronal death with features of apoptosis and necrosis: mediation by free radicals. Neuroscience 89(1):175-182
62. Klepper J, Voit T (2002) Facilitated glucose transporter protein type 1 (GLUT1) deficiency syndrome: impaired glucose transport into brain- a review. Eur J Pediatr 161(6):295-304
63. Laffel L (1999) Ketone bodies: a review of physiology, pathophysiology and application of monitoring to diabetes. Diabetes Metab Res Rev 15(6):412-426
64. Lebon V, Petersen KF, Cline GW (2002) Astroglial contribution to brain energy metabolism in humans revealed by 13C nuclear magnetic resonance spectroscopy: elucidation of the dominant pathway for neurotransmitter glutamate repletion and measurement of astrocytic oxidative metabolism. J Neurosci 22(5):1523-1531
65. Lee K, Berthiaume F, Stephanopoulos GN, Yarmush ML (1999) Metabolic flux analysis: a powerful tool for monitoring tissue function. Tissue Eng 5(4):347-368
66. Lewis LD, Ljunggren B, Norberg K, Siesjo BK (1974a) Changes in carbohydrate substrates, amino acids and ammonia in the brain during insulin-induced hypoglycemia. J Neurochem 23(4):659-671
67. Lewis LD, Ljunggren B, Ratcheson RA, Siesjo BK (1974b) Cerebral energy state in insulin-induced hypoglycemia, related to blood glucose and to EEG. J Neurochem 23(4):673-679
68. Magistretti P (2004) Brain Energy Metabolism. in J. Byrne and J. Roberts (eds) From Molecules to Networks. An Introduction to Cellular and Molecular Neuroscience: Elsevier Academic Press, 67-90
69. Magistretti PJ, 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(1387):1155-1163
70. Mangia S, Simpson IA, Vannucci SJ, Carruthers A (2009) The in vivo neuron-to-astrocyte lactate shuttle in human brain: evidence from modeling of measured lactate levels during visual stimulation. J Neurochem 109(Suppl 1):55-62
71. Mason GF, Rothman DL, Behar KL, Shulman RG (1992) NMR determination of the TCA cycle rate and alpha-ketoglutarate/glutamate exchange rate in rat brain. J Cereb Blood Flow Metab 12(3):434-447
72. Mason GF, Petersen KF, Lebon V, Rothman DL, Shulman GI (2006) Increased brain monocarboxylic acid transport and utilization in type 1 diabetes. Diabetes 55(4):929-934
73. Mason GF, Petersen KF, de Graaf RA, Shulman GI, Rothman DL (2007) Measurements of the anaplerotic rate in the human cerebral cortex using 13C magnetic resonance spectroscopy and [1-13C] and [2-13C] glucose. J Neurochem 100(1):73-86
74. Massieu L, Haces ML, Montiel T, Hernandez-Fonseca K (2003) Acetoacetate protects hippocampal neurons against glutamate-mediated neuronal damage during glycolysis inhibition. Neuroscience 120(2):365-378
75. McCrimmon RJ, Frier BM (1994) Hypoglycaemia, the most feared complication of insulin therapy. Diabete Metab 20(6):503-512
76. McKenna MC (2007) The glutamate-glutamine cycle is not stoichiometric: fates of glutamate in brain. J Neurosci Res 85(15):3347-3358
77. McKenna MC, Stevenson JH, Huang X, Hopkins IB (2000) Differential distribution of the enzymes glutamate dehydrogenase and aspartate aminotransferase in cortical synaptic mitochondria contributes to metabolic compartmentation in cortical synaptic terminals. Neurochem Int 37(2-3):229-241
78. McKenna M, Gruetter R, Sonnewald U, Waagepetersen H, Schousboe A (2006a) Energy Metabolism of the Brain. in N. Bazan (eds) Basic Neurochemistry: Molecular, Cellular and Medical Aspects: Elsevier Academic Press, 531-557
79. McKenna MC, Waagepetersen HS, Schousboe A, Sonnewald U (2006b) Neuronal and astrocytic shuttle mechanisms for cytosolic-mitochondrial transfer of reducing equivalents: current evidence and pharmacological tools. Biochem Pharmacol 71(4):399-407
80. Mejia-Toiber J, Montiel T, Massieu L (2006) D-beta-hydroxybutyrate prevents glutamate-mediated lipoperoxidation and neuronal damage elicited during glycolysis inhibition in vivo. Neurochem Res 31(12):1399-1408
81. Merle M, Martin M, Villegier A, Canioni P (1996) Mathematical modelling of the citric acid cycle for the analysis of glutamine isotopomers from cerebellar astrocytes incubated with [1(-13)C]glucose. Eur J Biochem 239(3):742-751
82. Morgenthaler FD, van Heeswijk RB, Xin L et al (2008) Non-invasive quantification of brain glycogen absolute concentration. J Neurochem 107(5):1414-1423
83. Morris AA (2005) Cerebral ketone body metabolism. J Inherit Metab Dis 28(2):109-121
84. Nehlig A (1997) Cerebral energy metabolism, glucose transport and blood flow: changes with maturation and adaptation to hypoglycaemia. Diabetes Metab 23(1):18-29
85. Nehlig A (2004) Brain uptake and metabolism of ketone bodies in animal models. Prostaglandins Leukot Essent Fat Acids 70(3):265-275
86. Nehlig A, Pereira de Vasconcelos A (1993) Glucose and ketone body utilization by the brain of neonatal rats. Prog Neurobiol 40(2):163-221
87. Nehlig A, Wittendorp-Rechenmann E, Lam CD (2004) Selective uptake of [14C]2-deoxyglucose by neurons and astrocytes: high-resolution microautoradiographic imaging by cellular 14C-trajectography combined with immunohistochemistry. J Cereb Blood Flow Metab 24(9):1004-1014
88. Nielsen J (1998) Metabolic engineering: techniques for analysis of targets for genetic manipulations. Biotechnol Bioeng 58(2-3):125-132
89. Niklas J, Schneider K, Heinzle E (2010) Metabolic flux analysis in eukaryotes. Curr Opin Biotechnol 21(1):63-69
90. Noh KM, Koh JY (2000) Induction and activation by zinc of NADPH oxidase in cultured cortical neurons and astrocytes. J Neurosci 20(23):RC111
91. Norberg K, Siesio BK (1976) Oxidative metabolism of the cerebral cortex of the rat in severe insulin-induced hypoglycaemia. J Neurochem 26(2):345-352
92. Okada Y, Lipton P (2007) Glucose, Oxidative Energy Metabolism, and Neural Function in Brain Slices - Glycolysis Plays a Key Role in Neural Activity. In G. Dienel and G. Gibson (eds) Brain Energetics. Integration of Molecular and Cellular Processes: Springer, 17-39
93. Olstad E, Olsen GM, Qu H, Sonnewald U (2007) Pyruvate recycling in cultured neurons from cerebellum. J Neurosci Res 85(15):3318-3325
94. Oz G, Henry PG, Seaquist ER, Gruetter R (2003) Direct, noninvasive measurement of brain glycogen metabolism in humans. Neurochem Int 43(4-5):323-329
95. Oz G, Seaquist ER, Kumar A et al (2007) Human brain glycogen content and metabolism: implications on its role in brain energy metabolism. Am J Physiol Endocrinol Metab 292(3):E946-E951
96. Oz G, Kumar A, Rao JP (2009) Human brain glycogen metabolism during and after hypoglycemia. Diabetes 58(9):1978-1985
97. Oz G, Tesfaye N, Kumar A, Deelchand DK, Eberly LE, Seaquist ER (2012) Brain glycogen content and metabolism in subjects with type 1 diabetes and hypoglycemia unawareness. J Cereb Blood Flow Metab 32(2):256-263
98. Page KA, Williamson A, Yu N et al (2009) Medium-chain fatty acids improve cognitive function in intensively treated type 1 diabetic patients and support in vitro synaptic transmission during acute hypoglycemia. Diabetes 58(5):1237-1244
99. Pan JW, de Graaf RA, Petersen KF, Shulman GI, Hetherington HP, Rothman DL (2002) [2,4-13 C2]-beta-Hydroxybutyrate metabolism in human brain. J Cereb Blood Flow Metab 22(7):890-898
100. Pellerin L (2010) Food for thought: the importance of glucose and other energy substrates for sustaining brain function under varying levels of activity. Diabetes Metab 36(Suppl 3):S59-S63
101. Pellerin L, Magistretti PJ (1994) Glutamate uptake into astrocytes stimulates aerobic glycolysis: a mechanism coupling neuronal activity to glucose utilization. Proc Natl Acad Sci U S A 91(22):10625-10629
102. Pellerin L, Pellegri G, Bittar PG (1998) Evidence supporting the existence of an activity-dependent astrocyte-neuron lactate shuttle. Dev Neurosci 20(4-5):291-299
103. Pellerin L, Bouzier-Sore AK, Aubert A et al (2007) Activity-dependent regulation of energy metabolism by astrocytes: an update. Glia 55(12):1251-1262
104. Quek LE, Dietmair S, Kromer JO, Nielsen LK (2010) Metabolic flux analysis in mammalian cell culture. Metab Eng 12(2):161-171
105. Rafiki A, Boulland JL, Halestrap AP, Ottersen OP, Bergersen L (2003) Highly differential expression of the monocarboxylate transporters MCT2 and MCT4 in the developing rat brain. Neuroscience 122(3):677-688
106. Raichle ME, Mintun MA (2006) Brain work and brain imaging. Annu Rev Neurosci 29:449-476
107. Rao R, Ennis K, Long JD, Ugurbil K, Gruetter R, Tkac I (2010) Neurochemical changes in the developing rat hippocampus during prolonged hypoglycemia. J Neurochem 114(3):728-738
108. Roberts EJ (2007) The support of energy metabolism in the central nervous system with substrates other than glucose. In G. Dienel and G. Gibson (eds) Brain energetics. Integration of molecular and cellular processes. Springer, Heidelberg, pp 197-238
109. Sensi SL, Yin HZ, Carriedo SG, Rao SS, Weiss JH (1999) Preferential Zn2+ influx through Ca2+ - permeable AMPA/kainate channels triggers prolonged mitochondrial superoxide production. Proc Natl Acad Sci U S A 96(5):2414-2419
110. Shen J, Rothman DL, Behar KL, Xu S (2009) Determination of the glutamate-glutamine cycling flux using two-compartment dynamic metabolic modeling is sensitive to astroglial dilution. J Cereb Blood Flow Metab 29(1):108-118
111. Shetty PK, Sadgrove MP, Galeffi F, Turner DA (2012) Pyruvate incubation enhances glycogen stores and sustains neuronal function during subsequent glucose deprivation. Neurobiol Dis 45(1):177-187
112. Sibson NR, Mason GF, Shen J et al (2001) In vivo (13)C NMR measurement of neurotransmitter glutamate cycling, anaplerosis and TCA cycle flux in rat brain during. J Neurochem 76(4):975-989
113. Simpson IA, Carruthers A, Vannucci SJ (2007) Supply and demand in cerebral energy metabolism: the role of nutrient transporters. J Cereb Blood Flow Metab 27(11):1766-1791
114. Sonnewald U, Westergaard N, Jones P, Taylor A, Bachelard HS, Schousboe A (1996) Metabolism of [U-13C5] glutamine in cultured astrocytes studied by NMR spectroscopy: first evidence of astrocytic pyruvate recycling. J Neurochem 67(6):2566-2572
115. Suh SW, Aoyama K, Chen Y et al (2003) Hypoglycemic neuronal death and cognitive impairment are prevented by poly(ADP-ribose) polymerase inhibitors administered after hypoglycemia. J Neurosci 23(33):10681-10690
116. Suh SW, Garnier P, Aoyama K, Chen Y, Swanson RA (2004) Zinc release contributes to hypoglycemia-induced neuronal death. Neurobiol Dis 16(3):538-545
117. Suh SW, Aoyama K, Matsumori Y, Liu J, Swanson RA (2005) Pyruvate administered after severe hypoglycemia reduces neuronal death and cognitive impairment. Diabetes 54(5):1452-1458
118. Suh SW, Bergher JP, Anderson CM, Treadway JL, Fosgerau K, Swanson RA (2007a) Astrocyte glycogen sustains neuronal activity during hypoglycemia:studies with the glycogen phosphorylase inhibitor CP-316,819. J Pharmacol Exp Ther
119. Suh SW, Hamby AM, Swanson RA (2007b) Hypoglycemia, brain energetics, and hypoglycemic neuronal death. Glia 55(12):1280-1286
120. Sutherland GR, Tyson RL, Auer RN (2008) Truncation of the krebs cycle during hypoglycemic coma. Med Chem 4(4):379-385
121. Suzuki A, Stern Sarah A, Bozdagi O et al (2011) Astrocyte-neuron lactate transport is required for long-term memory formation. Cell 144(5):810-823
122. Teixeira AP, Santos SS, Carinhas N, Oliveira R, Alves PM (2008) Combining metabolic flux analysis tools and 13C NMR to estimate intracellular fluxes of cultured astrocytes. Neurochem Int 52(3):478-486
123. Tekkok SB, Brown AM, Westenbroek R, Pellerin L, Ransom BR (2005) Transfer of glycogen-derived lactate from astrocytes to axons via specific monocarboxylate transporters supports mouse optic nerve activity. J Neurosci Res 81(5):644-652
124. Vallino JJ, Stephanopoulos G (1993) Metabolic flux distributions in Corynebacterium glutamicum during growth and lysine overproduction. Biotechnol Bioeng 41(6):633-646
125. Vannucci SJ, Simpson IA (2003) Developmental switch in brain nutrient transporter expression in the rat. Am J Physiol Endocrinol Metab 285(5):E1127-E1134
126. Varma A, Palsson BO (1994) Stoichiometric flux balance models quantitatively predict growth and metabolic by-product secretion in wild-type Escherichia coli W3110. Appl Environ Microbiol 60(10):3724-3731
127. Vavaiya KV, Briski KP (2008a) Effects of caudal fourth ventricular lactate infusion on hypoglycemia-associated MCT2, GLUT3, GLUT4, GCK, and sulfonylurea receptor-1 gene expression in the ovariectomized female rat LHA and VMH: impact of estradiol. J Mol Neurosci 34(2):121-129
128. Vavaiya KV, Briski KP (2008b) Effects of caudal hindbrain lactate infusion on insulin-induced hypoglycemia and neuronal substrate transporter glucokinase and sulfonylurea receptor-1 gene expression in the ovariectomized female rat dorsal vagal complex: Impact of estradiol. J Neurosci Res 86(3):694-701
129. Vavaiya KV, Paranjape SA, Patil GD, Briski KP (2006) Vagal complex monocarboxylate transporter-2 expression during hypoglycemia. Neuroreport 17(10):1023-1026
130. Waagepetersen HS, Qu H, Hertz L, Sonnewald U, Schousboe A (2002) Demonstration of pyruvate recycling in primary cultures of neocortical astrocytes but not in neurons. Neurochem Res 27(11):1431-1437
131. Wada H, Okada Y, Nabetani M, Nakamura H (1997) The effects of lactate and beta-hydroxybutyrate on the energy metabolism and neural activity of hippocampal slices from adult and immature rat. Brain Res Dev Brain Res 101(1-2):1-7
132. Warren RE, Frier BM (2005) Hypoglycaemia and cognitive function. Diabetes Obes Metab 7(5):493-503
133. Wender R, Brown AM, Fern R, Swanson RA, Farrell K, Ransom BR (2000) Astrocytic glycogen influences axon function and survival during glucose deprivation in central white matter. J Neurosci 20(18):6804-6810
134. Wiechert W (2001) 13C metabolic flux analysis. Metab Eng 3(3):195-206
135. Wieloch T (1985) Hypoglycemia-induced neuronal damage prevented by an N-methyl-D-aspartate antagonist. Science 230(4726):681-683
136. Wieloch T, Harris RJ, Symon L, Siesjo BK (1984) Influence of severe hypoglycemia on brain extracellular calcium and potassium activities, energy, and phospholipid metabolism. J Neurochem 43(1):160-168
137. Williams LR, Leggett RW (1989) Reference values for resting blood flow to organs of man. Clin Phys Physiol Meas 10(3):187-217
138. Yamada KA, Rensing N, Thio LL (2005) Ketogenic diet reduces hypoglycemia-induced neuronal death in young rats. Neurosci Lett 385(3):210-214
139. Yamane K, Yokono K, Okada Y (2000) Anaerobic glycolysis is crucial for the maintenance of neural activity in guinea pig hippocampal slices. J Neurosci Methods 103(2):163-171
140. Zhou D, Qian J, Chang H, Xi B, Sun RP (2012) Pyruvate administered to newborn rats with insulin-induced hypoglycemic brain injury reduces neuronal death and cognitive impairment. Eur J Pediatr 171(1):103-109
141. Zhu PJ, Krnjevic K (1993) Adenosine release is a major cause of failure of synaptic transmission during hypoglycaemia in rat hippocampal slices. Neurosci Lett 155(2):128-131
142. Zielke HR, Zielke CL, Baab PJ (2009) Direct measurement of oxidative metabolism in the living brain by microdialysis: a review. J Neurochem 109(Suppl 1):24-29
143. Zwingmann C, Leibfritz D (2007) Glial-Neuronal shuttle systems. In G. Dienel and G. Gibson (eds) Brain energetics. Integration of molecular and cellular processes. Springer, Heidelberg, pp 197-238