The metabolic trinity, glucose–glycogen–lactate, links astrocytes and neurons in brain energetics, signaling, memory, and gene expression

Neuroscience Letters

Volumn 637, Issue , 2017, Pages 18-25

  Dienel, Gerald A ^a  

^a UNIVERSITY OF ARKANSAS FOR MEDICAL SCIENCES   (United States)

Author keywords

Astrocyte; Glucose; Glycogen; Lactate; Neuron

Indexed keywords

CARBOHYDRATE; CARBOXYLIC ACID; GLUCOSE; GLYCOGEN; LACTIC ACID;

ADRENERGIC ACTIVITY; AEROBIC GLYCOLYSIS; ARTICLE; ASTROCYTE; BLOOD; BRAIN; ENERGY TRANSFER; EXERCISE; GENE EXPRESSION; GLUCOSE BLOOD LEVEL; GLUCOSE METABOLISM; GLYCOGEN METABOLISM; GLYCOGENOLYSIS; HUMAN; LOCUS CERULEUS; LYMPHATIC DRAINAGE; MEMORY; MEMORY CONSOLIDATION; NERVE CELL; NONHUMAN; OXYGEN CONSUMPTION; PRIORITY JOURNAL; ANIMAL; METABOLISM; PHYSIOLOGY;

ANIMALS; ASTROCYTES; BRAIN; GLUCOSE; HUMANS; LACTIC ACID; MEMORY; NEURONS;

EID: 84924125355     PISSN: 03043940     EISSN: 18727972     Source Type: Journal    
DOI: 10.1016/j.neulet.2015.02.052     Document Type: Article

References (71)

1. [1] Ball, K.K., Cruz, N.F., Mrak, R.E., Dienel, G.A., Trafficking of glucose, lactate, and amyloid-beta from the inferior colliculus through perivascular routes. J. Cereb. Blood Flow Metab. 30 (2010), 162–176.
2. [2] Bergersen, L.H., Lactate transport and signaling in the brain: potential therapeutic targets and roles in body–brain interaction. J Cereb. Blood Flow Metab. 35:February (2) (2015), 176–185.
3. [3] Bouzat, P., Sala, N., Suys, T., Zerlauth, J.B., Marques-Vidal, P., Feihl, F., Bloch, J., Messerer, M., Levivier, M., Meuli, R., Magistretti, P.J., Oddo, M., Cerebral metabolic effects of exogenous lactate supplementation on the injured human brain. Intensive Care Med. 40 (2014), 412–421.
4. [4] Bozzo, L., Puyal, J., Chatton, J.Y., Lactate modulates the activity of primary cortical neurons through a receptor-mediated pathway. PLoS One, 8, 2013, e71721.
5. [5] Bradbury, M.W.B., Cserr, H.F., Drainage of cerebral interstitial fluid and of cerebrospinal fluid into lymphatics. Johnston, M.G., (eds.) Experimental Biology of the Lymphatic Circulation, 1985, Elsevier, New York, 355–394.
6. [6] Caesar, K., Hashemi, P., Douhou, A., Bonvento, G., Boutelle, M.G., Walls, A.B., Lauritzen, M., Glutamate receptor-dependent increments in lactate, glucose and oxygen metabolism evoked in rat cerebellum in vivo. J. physiol. 586 (2008), 1337–1349.
7. [7] Cremer, J.E., Heath, D.F., The estimation of rates of utilization of glucose and ketone bodies in the brain of the suckling rat using compartmental analysis of isotopic data. Biochem. J. 142 (1974), 527–544.
8. +-induced spreading cortical depression. J. Cereb. Blood Flow Metab. 19 (1999), 380–392.
9. [9] Cruz, N.F., Ball, K.K., Dienel, G.A., Functional imaging of focal brain activation in conscious rats: impact of [(14)C] glucose metabolite spreading and release. J. Neurosci. Res. 85 (2007), 3254–3266.
10. 14C] glucose metabolism during brain activation of α-syntrophin knockout mice. J. Neurochem. 125 (2013), 247–259.
11. [11] Dienel, G.A., Astrocytic energetics during excitatory neurotransmission: what are contributions of glutamate oxidation and glycolysis?. Neurochem. Int. 63 (2013), 244–258.
12. [12] Dienel, G.A., Brain lactate metabolism: the discoveries and the controversies. J. Cereb. Blood Flow Metab. 32 (2012), 1107–1138.
13. [13] Dienel, G.A., Fueling and imaging brain activation. ASN Neuro, 4(5), 2012, 10.01042/AN20120021 pii: e00093.
14. [14] Dienel, G.A., Lactate shuttling and lactate use as fuel after traumatic brain injury: metabolic considerations. J. Cereb. Blood Flow Metab. 34 (2014), 1736–1748.
15. [15] Dienel, G.A., Cruz, N.F., Contributions of glycogen to astrocytic energetics during brain activation. Metab. Brain Dis. 30 (2015), 281–298.
16. [16] Dienel, G.A., Cruz, N.F., Mori, K., Holden, J.E., Sokoloff, L., Direct measurement of the lambda of the lumped constant of the deoxyglucose method in rat brain: determination of lambda and lumped constant from tissue glucose concentration or equilibrium brain/plasma distribution ratio for methylglucose. J. Cereb. Blood Flow Metab. 11 (1991), 25–34.
17. [17] Dienel, G.A., Hertz, L., Glucose and lactate metabolism during brain activation. J. Neurosci. Res. 66 (2001), 824–838.
18. [18] Ding, F., O'Donnell, J., Thrane, A.S., Zeppenfeld, D., Kang, H., Xie, L., Wang, F., Nedergaard, M., alpha1-adrenergic receptors mediate coordinated Ca(2+) signaling of cortical astrocytes in awake, behaving mice. Cell Calcium 54 (2013), 387–394.
19. [19] DiNuzzo, M., Mangia, S., Maraviglia, B., Giove, F., Glycogenolysis in astrocytes supports blood-borne glucose channeling not glycogen-derived lactate shuttling to neurons: evidence from mathematical modeling. J. Cereb. Blood Flow Metab. 30 (2010), 1895–1904.
20. [20] Duran, J., Saez, I., Gruart, A., Guinovart, J.J., Delgado-Garcia, J.M., Impairment in long-term memory formation and learning-dependent synaptic plasticity in mice lacking glycogen synthase in the brain. J. Cereb. Blood Flow Metab. 33 (2013), 550–556.
21. [21] Eichling, J.O., Raichle, M.E., Grubb, R.L., Ter-Pogossian, M.M., Evidence of the limitations of water as a freely diffusible tracer in brain of the rhesus monkey. Circ. Res. 35 (1974), 358–364.
22. [22] Gandhi, G.K., Cruz, N.F., Ball, K.K., Dienel, G.A., Astrocytes are poised for lactate trafficking and release from activated brain and for supply of glucose to neurons. J. Neurochem. 111 (2009), 522–536.
23. [23] Gibbs, M.E., Hutchinson, D.S., Rapid turnover of glycogen in memory formation. Neurochem. Res. 37:November (11) (2012), 2456–2463.
24. [24] Gilbert, E., Tang, J.M., Ludvig, N., Bergold, P.J., Elevated lactate suppresses neuronal firing in vivo and inhibits glucose metabolism in hippocampal slice cultures. Brain Res. 1117 (2006), 213–223.
25. [25] Ginsberg, M.D., Busto, R., Harik, S.I., Regional blood-brain barrier permeability to water and cerebral blood flow during status epilepticus: insensitivity to norepinephrine depletion. Brain Res. 337 (1985), 59–71.
26. [26] Gold, P.E., Newman, L.A., Scavuzzo, C.J., Korol, D.L., Modulation of multiple memory systems: from neurotransmitters to metabolic substrates. Hippocampus 23 (2013), 1053–1065.
27. [27] Harik, S.I., Busto, R., Martinez, E., Norepinephrine regulation of cerebral glycogen utilization during seizures and ischemia. J. Neurosci. 2 (1982), 409–414.
28. [28] Heath, D.F., Rose, J.G., The distribution of glucose and [14C] glucose between erythrocytes and plasma in the rat. Biochem. J. 112 (1969), 373–377.
29. [29] Hertz, L., Chen, Y., Gibbs, M.E., Zang, P., Peng, L., Astrocytic adrenoceptors: a major drug target in neurological and psychiatric disorders?. Curr. Drug Targets CNS Neurol. Disord. 3 (2004), 239–267.
30. [30] Hertz, L., Dienel, G.A., Lactate transport and transporters: general principles and functional roles in brain cells. J. Neurosci. Res. 79 (2005), 11–18.
31. [31] Hertz, L., Gibbs, M.E., Dienel, G.A., Fluxes of lactate into, from, and among gap junction-coupled astrocytes and their interaction with noradrenaline. Front. Neurosci., 8, 2014, 261.
32. [32] Hertz, L., Lovatt, D., Goldman, S.A., Nedergaard, M., Adrenoceptors in brain: cellular gene expression and effects on astrocytic metabolism and [Ca(2+)]i. Neurochem. Int. 57 (2010), 411–420.
33. [33] Hertz, L., Xu, J., Song, D., Du, T., Li, B., Yan, E., Peng, L., Astrocytic glycogenolysis: mechanisms and functions. Metab. Brain Dis. 30 (2015), 317–333.
34. [34] Hertz, L., Xu, J., Song, D., Du, T., Yan, E., Peng, L., Brain glycogenolysis, adrenoceptors, pyruvate carboxylase, Na(+), K(+)-ATPase and Marie E. Gibbs’ pioneering learning studies. Front. Integr. Neurosci., 7, 2013, 20.
35. [35] Ingvar, M., Lindvall, O., Folbergrova, J., Siesjo, B.K., Influence of lesions of the noradrenergic locus coeruleus system on the cerebral metabolic response to bicuculline-induced seizures. Brain Res. 264 (1983), 225–231.
36. [36] Justice, A., Feldman, S.M., Brown, L.L., The nucleus locus coeruleus modulates local cerebral glucose utilization during noise stress in rats. Brain Res. 490 (1989), 73–84.
37. [37] Kauppinen, R.A., Nicholls, D.G., Failure to maintain glycolysis in anoxic nerve terminals. J. Neurochem. 47 (1986), 1864–1869.
38. [38] Kogure, K., Scheinberg, P., Kishikawa, H., Utsunomiya, Y., Busto, R., Adrenergic control of cerebral blood flow and energy metabolism in the rat. Stroke J. Cereb. Circ. 10 (1979), 179–184.
39. [39] Lauritzen, K.H., Morland, C., Puchades, M., Holm-Hansen, S., Hagelin, E.M., Lauritzen, F., Attramadal, H., Storm-Mathisen, J., Gjedde, A., Bergersen, L.H., Lactate receptor sites link neurotransmission, neurovascular coupling, and brain energy metabolism. Cereb. Cortex 24 (2014), 2784–2795.
40. [40] Levin, B.E., Craik, R.L., Hand, P.J., The role of norepinephrine in adult rat somatosensory (SmI) cortical metabolism and plasticity. Brain Res. 443 (1988), 261–271.
41. [41] Lind, K.R., Ball, K.K., Cruz, N.F., Dienel, G.A., The unfolded protein response to endoplasmic reticulum stress in cultured astrocytes and rat brain during experimental diabetes. Neurochem. Int. 62 (2013), 784–795.
42. [42] Lipski, W.J., Grace, A.A., Footshock-induced responses in ventral subiculum neurons are mediated by locus coeruleus noradrenergic afferents. Eur. Neuropsychopharmacol. 23 (2013), 1320–1328.
43. [43] MacAulay, N., Zeuthen, T., Water transport between CNS compartments: contributions of aquaporins and cotransporters. Neuroscience 168 (2010), 941–956.
44. [44] Matsui, T., Soya, S., Okamoto, M., Ichitani, Y., Kawanaka, K., Soya, H., Brain glycogen decreases during prolonged exercise. J. Physiol. 589 (2011), 3383–3393.
45. [45] McKenna, M.C., Glutamate pays its own way in astrocytes. Front. Endocrinol., 4, 2013.
46. [46] Muller, M.S., Functional impact of glycogen degradation on astrocytic signalling. Biochem. Soc. Trans. 42 (2014), 1311–1315.
47. [47] Nasrallah, F.A., Garner, B., Ball, G.E., Rae, C., Modulation of brain metabolism by very low concentrations of the commonly used drug delivery vehicle dimethyl sulfoxide (DMSO). J. Neurosci. Res. 86 (2008), 208–214.
48. [48] Newman, L.A., Korol, D.L., Gold, P.E., Lactate produced by glycogenolysis in astrocytes regulates memory processing. PLoS One, 6, 2011, e28427.
49. [49] O'Donnell, J., Zeppenfeld, D., McConnell, E., Pena, S., Nedergaard, M., Norepinephrine: a neuromodulator that boosts the function of multiple cell types to optimize CNS performance. Neurochem. Res. 37:November (11) (2012), 2496–2512.
50. [50] Obel, L.F., Andersen, K.M., Bak, L.K., Schousboe, A., Waagepetersen, H.S., Effects of adrenergic agents on intracellular Ca(2+) homeostasis and metabolism of glucose in astrocytes with an emphasis on pyruvate carboxylation, oxidative decarboxylation and recycling: implications for glutamate neurotransmission and excitotoxicity. Neurotox. Res. 21 (2012), 405–417.
51. [51] Obel, L.F., Muller, M.S., Walls, A.B., Sickmann, H.M., Bak, L.K., Waagepetersen, H.S., Schousboe, A., Brain glycogen-new perspectives on its metabolic function and regulation at the subcellular level. Front. Neuroenerg., 4, 2012, 3.
52. [52] Patel, A.B., Lai, J.C., Chowdhury, G.M., Hyder, F., Rothman, D.L., Shulman, R.G., Behar, K.L., Direct evidence for activity-dependent glucose phosphorylation in neurons with implications for the astrocyte-to-neuron lactate shuttle. Proc. Natl. Acad. Sci. U. S. A. 111 (2014), 5385–5390.
53. [53] Pellerin, L., Magistretti, P.J., Glutamate uptake into astrocytes stimulates aerobic glycolysis: a mechanism coupling neuronal activity to glucose utilization. Proc. Natl. Acad. Sci. U. S. A. 91 (1994), 10625–10629.
54. [54] Pellerin, L., Magistretti, P.J., Sweet sixteen for ANLS. J. Cereb. Blood Flow Metab. 32 (2012), 1152–1166.
55. [55] Quistorff, B., Secher, N.H., Van Lieshout, J.J., Lactate fuels the human brain during exercise. FASEB J. 22 (2008), 3443–3449.
56. [56] Raichle, M.E., Hartman, B.K., Eichling, J.O., Sharpe, L.G., Central noradrenergic regulation of cerebral blood flow and vascular permeability. Proc. Natl. Acad. Sci. U. S. A. 72 (1975), 3726–3730.
57. [57] Rasmussen, P., Wyss, M.T., Lundby, C., Cerebral glucose and lactate consumption during cerebral activation by physical activity in humans. Faseb J. 25 (2011), 2865–2873.
58. [58] Rennels, M.L., Gregory, T.F., Blaumanis, O.R., Fujimoto, K., Grady, P.A., Evidence for a ‘paravascular’ fluid circulation in the mammalian central nervous system, provided by the rapid distribution of tracer protein throughout the brain from the subarachnoid space. Brain Res. 326 (1985), 47–63.
59. [59] Savaki, H.E., Graham, D.I., Grome, J.J., McCulloch, J., Functional consequences of unilateral lesion of the locus coeruleus: a quantitative [14C]2-deoxyglucose investigation. Brain Res. 292 (1984), 239–249.
60. [60] Savaki, H.E., Kadekaro, M., McCulloch, J., Sokoloff, L., The central noradrenergic system in the rat: metabolic mapping with alpha-adrenergic blocking agents. Brain Res. 234 (1982), 65–79.
61. [61] Seifert, T., Secher, N.H., Sympathetic influence on cerebral blood flow and metabolism during exercise in humans. Prog. Neurobiol. 95 (2011), 406–426.
62. [62] Siesjö, B.K., Brain Energy Metabolism. 1978, John Wiley & Sons, Chichester.
63. [63] Spray, D.C., Iacobas, D.A., Organizational principles of the connexin-related brain transcriptome. J. Membr. Biol. 218 (2007), 39–47.
64. [64] Suzuki, A., Stern, S.A., Bozdagi, O., Huntley, G.W., Walker, R.H., Magistretti, P.J., Alberini, C.M., Astrocyte-neuron lactate transport is required for long-term memory formation. Cell 144 (2011), 810–823.
65. [65] Tang, F., Lane, S., Korsak, A., Paton, J.F., Gourine, A.V., Kasparov, S., Teschemacher, A.G., Lactate-mediated glia-neuronal signalling in the mammalian brain. Nat. Commun., 5, 2014, 3284.
66. [66] Vissing, J., Andersen, M., Diemer, N.H., Exercise-induced changes in local cerebral glucose utilization in the rat. J. Cereb. Blood Flow Metab. 16 (1996), 729–736.
67. [67] Walz, W., Mukerji, S., Lactate release from cultured astrocytes and neurons: a comparison. Glia 1 (1988), 366–370.
68. [68] Wilhelm, F., Hirrlinger, J., Multifunctional Roles of NAD(+) and NADH in Astrocytes. Neurochem. Res. 37 (2012), 2317–2325.
69. + and NADH content. J. Neurosci. Res. 89 (2011), 1956–1964.
70. [70] Yang, J., Ruchti, E., Petit, J.-M., Jourdain, P., Grenningloh, G., Allaman, I., Magistretti, P.J., Lactate promotes plasticity gene expression by potentiating NMDA signaling in neurons. Proc. Natl. Acad. Sci. 111 (2014), 12228–12233.
71. 2+ as a signalling route. ASN Neuro, 4, 2012, 10.01042/AN20110061 pii: e00080.