Glycogenolysis in Cerebral Cortex During Sensory Stimulation, Acute Hypoglycemia, and Exercise: Impact on Astrocytic Energetics, Aerobic Glycolysis, and Astrocyte-Neuron Interactions

Dienel, Gerald A.; Rothman, Douglas L.

doi:10.1007/978-3-030-27480-1_8

Gerald A. Dienel^4,5 &
Douglas L. Rothman⁶

Part of the book series: Advances in Neurobiology ((NEUROBIOL,volume 23))

1407 Accesses
20 Citations

Abstract

Most glycogen in cerebral cortex is located in astrocytes, and the importance of glycogenolysis for critical functions, including neurotransmission and memory consolidation, is strongly supported by many studies. However, specific mechanisms through which glycogen sustains essential functions remain to be established by rigorous, quantitative studies. Cerebral cortical glycogen concentrations are in the range of 10–12 μmol/g in carefully-handled animals, and the calculated rate of glycogenolysis (CMR_glycogen) during sensory stimulation is approximately 60% that of glucose utilization (CMR_glc) by all cells, with lower rates during acute hypoglycemia and exercise to exhaustion. CMR_glycogen is at least fourfold higher when the volume fraction of astrocytes is taken into account. Inclusion of glycogen consumed during sensory stimulation in calculation of the oxygen-glucose index (OGI = CMR_O2/CMR_glc, which has a theoretical maximum of 6 when no other substrates are metabolized) reduces OGI from 5.0 to 2.8. Thus, at least 53% of the carbohydrate is not oxidized, suggesting that glycogen mobilization supports astrocytic glycolysis, not neuronal oxidation of glycogen-derived lactate that would cause OGI to exceed 6. Failure of glycogenolysis to dilute the specific activity of lactate formed from blood-borne [6-¹⁴C]glucose indicates compartmentation of glycolytic metabolism of glucose and glycogen and the rapid release from cerebral cortex of glycogen-derived lactate. Together, these findings invalidate the conclusion by others that glycogen-derived lactate is a major fuel for neurons during neurotransmission, memory consolidation, and exercise to exhaustion. Alternative mechanisms, including glucose sparing for neurons, are presented as testable explanations for data interpreted as lactate shuttling.

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Abbreviations

(A-V)_substrate:: Arteriovenous difference across the brain for the identified substrate
Asp:: Aspartate
BAY U6751:: 4-(2-Chlorophenyl)-l-ethyl-1,4-dihydro-6-methyl-2,3,5-pyridinetricarboxylic acid 5-isopropyl ester disodium salt hydrate
CBF:: Cerebral blood flow rate
CMR:: Cerebral metabolic rate for substrate of interest = CBF(A-V)_substrate
CMR_glc:: Cerebral metabolic rate for glucose = CBF(A-V)_glc
CMR_glycogen:: Cerebral metabolic rate for glycogen = Δ[glycogen]/time
CMR_O2:: Cerebral metabolic rate for oxygen CBF(A-V)_O2
CP-316,819:: [R-R∗,S∗]-5-chloro-N-[2-hydroxy-3-(methoxymethylamino)-3-oxo-l-(phenylmethyl)propyl]-1H-indole-2-carboxamide
DAB:: 1,4-Dideoxy-1,4-imino-d-arabinitol
DG:: 2-deoxy-d-glucose
DMSO:: Dimethyl sulfoxide
FDG:: 2-fluoro-2-deoxy-d-glucose
Glc:: Glucose
Glc-6-P:: Glucose-6-phosphate
Gln:: Glutamine
Glu:: Glutamate
GLUT:: Glucose transporter; GLUT1 in vascular endothelium and astrocytes, and GLUT3 and GLUT4 in neurons
GPR81:: G-protein-coupled lactate receptor81, also known as HCAR1
HCAR1:: Hydroxycarboxylic acid receptor1 also known as GPR81
KO:: Knockout
Lac:: Lactate
LTP:: Long-term potentiation
MCT:: Monocarboxylic acid transporter; MCT1 and MCT4 isoforms are mainly astrocytic, whereas MCT2 is predominantly neuronal
NMDA:: N-Methyl-d-aspartate
OCI:: Oxygen carbohydrate index = CMR_O2/[CMR_glc + 0.5CMR_lac + CMR_glycogen] = (A-V)_O2/((A-V)_glc + 0.5(A-V)_lac + Δ[glycogen]), where lactate and [glycogen] are expressed in glucosyl units (2Lac = 1Glc)
OGI:: Oxygen-glucose index = CMR_O2/CMR_glc = (A-V)_O2/(A-V)_glc (CBF cancels out). This calculation assumes no other substrates are oxidized
PAPs:: Peripheral astrocytic processes
RSA:: Relative specific activity (SA) = ratio of the SA of a compound of interest to the SA of a reference compound, e.g., SA lactate/SA glucose
SA:: Specific activity (dpm/μmol)
TCA:: Tricarboxylic acid

References

Adachi K, Cruz NF, Sokoloff L, Dienel GA (1995) Labeling of metabolic pools by [6-¹⁴C]glucose during K(+)-induced stimulation of glucose utilization in rat brain. J Cereb Blood Flow Metab 15(1):97–110. https://doi.org/10.1038/jcbfm.1995.11
Article CAS PubMed Google Scholar
Aiston S, Andersen B, Agius L (2003) Glucose 6-phosphate regulates hepatic glycogenolysis through inactivation of phosphorylase. Diabetes 52(6):1333–1339
Article CAS PubMed Google Scholar
Aiston S, Green A, Mukhtar M, Agius L (2004) Glucose 6-phosphate causes translocation of phosphorylase in hepatocytes and inactivates the enzyme synergistically with glucose. Biochem J 377(Pt 1):195–204. https://doi.org/10.1042/bj20031191
Article CAS PubMed PubMed Central Google Scholar
Alberini CM, Cruz E, Descalzi G, Bessières B, Gao V (2018) Astrocyte glycogen and lactate: New insights into learning and memory mechanisms. Glia 66(6):1244–1262. https://doi.org/10.1002/glia.23250
Article PubMed Google Scholar
Araque A, Parpura V, Sanzgiri RP, Haydon PG (1998a) Glutamate-dependent astrocyte modulation of synaptic transmission between cultured hippocampal neurons. Eur J Neurosci 10(6):2129–2142. https://doi.org/10.1046/j.1460-9568.1998.00221.x
Article CAS PubMed Google Scholar
Araque A, Sanzgiri RP, Parpura V, Haydon PG (1998b) Calcium elevation in astrocytes causes an NMDA receptor-dependent increase in the frequency of miniature synaptic currents in cultured hippocampal neurons. J Neurosci 18(17):6822–6829
Article CAS PubMed PubMed Central Google Scholar
Ashrafi G, Ryan TA (2017) Glucose metabolism in nerve terminals. Curr Opin Neurobiol 45:156–161. https://doi.org/10.1016/j.conb.2017.03.007
Article CAS PubMed PubMed Central Google Scholar
Ashrafi G, Wu Z, Farrell RJ, Ryan TA (2017) GLUT4 mobilization supports energetic demands of active synapses. Neuron 93(3):606–615.e603. https://doi.org/10.1016/j.neuron.2016.12.020
Article CAS PubMed PubMed Central Google Scholar
Bachelard HS, Goldfarb PS (1969) Adenine nucleotides and magnesium ions in relation to control of mammalian cerebral-cortex hexokinase. Biochem J 112(5):579–586
CAS PubMed PubMed Central Google Scholar
Bak LK, Schousboe A, Sonnewald U, Waagepetersen HS (2006) Glucose is necessary to maintain neurotransmitter homeostasis during synaptic activity in cultured glutamatergic neurons. J Cereb Blood Flow Metab 26(10):1285–1297. https://doi.org/10.1038/sj.jcbfm.9600281
Article CAS PubMed Google Scholar
Bak LK, Walls AB, Schousboe A, Ring A, Sonnewald U, Waagepetersen HS (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. https://doi.org/10.1111/j.1471-4159.2009.05943.x
Article CAS PubMed Google Scholar
Bak LK, Obel LF, Walls AB, Schousboe A, Faek SA, Jajo FS, Waagepetersen HS (2012) Novel model of neuronal bioenergetics: post-synaptic utilization of glucose but not lactate correlates positively with Ca2+ signaling in cultured mouse glutamatergic neurons. ASN Neuro 4(3):151–160. https://doi.org/10.1042/an20120004
Article CAS Google Scholar
Bak LK, Walls AB, Schousboe A, Waagepetersen HS (2018) Astrocytic glycogen metabolism in the healthy and diseased brain. J Biol Chem 293(19):7108–7116. https://doi.org/10.1074/jbc.R117.803239
Article CAS PubMed PubMed Central Google Scholar
Ball KK, Cruz NF, Mrak RE, Dienel GA (2010) Trafficking of glucose, lactate, and amyloid-beta from the inferior colliculus through perivascular routes. J Cereb Blood Flow Metab 30(1):162–176. https://doi.org/10.1038/jcbfm.2009.206
Article CAS PubMed Google Scholar
Benveniste H, Dienel G, Jacob Z, Lee H, Makaryus R, Gjedde A, Hyder F, Rothman DL (2018) Trajectories of brain lactate and re-visited oxygen-glucose index calculations do not support elevated non-oxidative metabolism of glucose across childhood. Front Neurosci 12:631. https://doi.org/10.3389/fnins.2018.00631
Article PubMed PubMed Central Google Scholar
Boumezbeur F, Petersen KF, Cline GW, Mason GF, Behar KL, Shulman GI, Rothman DL (2010) The contribution of blood lactate to brain energy metabolism in humans measured by dynamic 13C nuclear magnetic resonance spectroscopy. J Neurosci 30(42):13983–13991. https://doi.org/10.1523/jneurosci.2040-10.2010
Article CAS PubMed PubMed Central Google Scholar
Bozzo L, Puyal J, Chatton JY (2013) Lactate modulates the activity of primary cortical neurons through a receptor-mediated pathway. PLoS One 8(8):e71721. https://doi.org/10.1371/journal.pone.0071721
Article CAS PubMed PubMed Central Google Scholar
Bröer S, Bröer A, Schneider HP, Stegen C, Halestrap AP, Deitmer JW (1999) Characterization of the high-affinity monocarboxylate transporter MCT2 in Xenopus laevis oocytes. Biochem J 341:529–535
Article PubMed PubMed Central Google Scholar
Cataldo AM, Broadwell RD (1986) Cytochemical identification of cerebral glycogen and glucose-6-phosphatase activity under normal and experimental conditions: I. Neurons and glia. J Electron Microsc Tech 3(4):413–437. https://doi.org/10.1002/jemt.1060030406
Article CAS Google Scholar
Choi IY, Seaquist ER, Gruetter R (2003) Effect of hypoglycemia on brain glycogen metabolism in vivo. J Neurosci Res 72(1):25–32. https://doi.org/10.1002/jnr.10574
Article CAS PubMed PubMed Central Google Scholar
Cornell-Bell AH, Finkbeiner SM, Cooper MS, Smith SJ (1990a) Glutamate induces calcium waves in cultured astrocytes: long-range glial signaling. Science 247(4941):470–473
Article CAS PubMed Google Scholar
Cornell-Bell AH, Thomas PG, Smith SJ (1990b) The excitatory neurotransmitter glutamate causes filopodia formation in cultured hippocampal astrocytes. Glia 3(5):322–334. https://doi.org/10.1002/glia.440030503
Article CAS PubMed Google Scholar
Crane RK, Sols A (1954) The non-competitive inhibition of brain hexokinase by glucose-6-phosphate and related compounds. J Biol Chem 210(2):597–606
CAS PubMed Google Scholar
Crerar MM, Karlsson O, Fletterick RJ, Hwang PK (1995) Chimeric muscle and brain glycogen phosphorylases define protein domains governing isozyme-specific responses to allosteric activation. J Biol Chem 270(23):13748–13756
Article CAS PubMed Google Scholar
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. https://doi.org/10.1097/00004647-200212000-00008
Article CAS PubMed Google Scholar
Cruz NF, Adachi K, Dienel GA (1999) Rapid efflux of lactate from cerebral cortex during K+ −induced spreading cortical depression. J Cereb Blood Flow Metab 19(4):380–392. https://doi.org/10.1097/00004647-199904000-00004
Article CAS PubMed Google Scholar
Cruz NF, Ball KK, Dienel GA (2007) Functional imaging of focal brain activation in conscious rats: impact of [(14)C]glucose metabolite spreading and release. J Neurosci Res 85(15):3254–3266. https://doi.org/10.1002/jnr.21193
Article CAS PubMed Google Scholar
Danchin A, Buc H (1973) Affinity labeling of the adenosine 5′-monophosphate binding site of rabbit muscle glycogen phosphorylase b with an adenosine 5′-monophosphate-cobalt(3) complex. J Biol Chem 248(9):3241–3247
CAS PubMed Google Scholar
Derouiche A, Frotscher M (1991) Astroglial processes around identified glutamatergic synapses contain glutamine synthetase: evidence for transmitter degradation. Brain Res 552(2):346–350
Article CAS PubMed Google Scholar
Derouiche A, Rauen T (1995) Coincidence of L-glutamate/L-aspartate transporter (GLAST) and glutamine synthetase (GS) immunoreactions in retinal glia: evidence for coupling of GLAST and GS in transmitter clearance. J Neurosci Res 42(1):131–143. https://doi.org/10.1002/jnr.490420115
Article CAS PubMed Google Scholar
Derouiche A, Haseleu J, Korf HW (2015) Fine astrocyte processes contain very small mitochondria: glial oxidative capability may fuel transmitter metabolism. Neurochem Res 40(12):2402–2413. https://doi.org/10.1007/s11064-015-1563-8
Article CAS PubMed Google Scholar
Diaz-Garcia CM, Yellen G (2019) Neurons rely on glucose rather than astrocytic lactate during stimulation. J Neurosci Res 97(8):883–889. https://doi.org/10.1002/jnr.24374
Article CAS PubMed Google Scholar
Diaz-Garcia CM, Mongeon R, Lahmann C, Koveal D, Zucker H, Yellen G (2017) Neuronal stimulation triggers neuronal glycolysis and not lactate uptake. Cell Metab 26(2):361–374. e364. https://doi.org/10.1016/j.cmet.2017.06.021
Article CAS PubMed PubMed Central Google Scholar
Dienel GA (2012) Fueling and imaging brain activation. ASN Neuro 4(5):267–321. art:e00093. https://doi.org/10.1042/an20120021
Article CAS Google Scholar
Dienel GA (2017a) Lack of appropriate stoichiometry: strong evidence against an energetically-important astrocyte-neuron lactate shuttle in brain. J Neurosci Res 95(11):2103–2125. https://doi.org/10.1002/jnr.24015
Article CAS PubMed Google Scholar
Dienel GA (2017b) The metabolic trinity, glucose–glycogen–lactate, links astrocytes and neurons in brain energetics, signaling, memory, and gene expression. Neurosci Lett 637:18–25. https://doi.org/10.1016/j.neulet.2015.02.052
Article CAS PubMed Google Scholar
Dienel GA (2019a) Brain glucose metabolism: Integration of energetics with function. Physiol Rev 99(1):949–1045. https://doi.org/10.1152/physrev.00062.2017
Article CAS PubMed Google Scholar
Dienel GA (2019b) Does shuttling of glycogen-derived lactate from astrocytes to neurons take place during neurotransmission and memory consolidation? J Neuro Res 97(8):863–882. https://doi.org/10.1002/jnr.24387
Article CAS Google Scholar
Dienel GA, Cruz NF (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):30–37. https://doi.org/10.1111/j.1471-4159.2009.05859.x
Article CAS PubMed PubMed Central Google Scholar
Dienel GA, Cruz NF (2016) Aerobic glycolysis during brain activation: adrenergic regulation and influence of norepinephrine on astrocytic metabolism. J Neurochem 138(1):14–52. https://doi.org/10.1111/jnc.13630
Article CAS PubMed Google Scholar
Dienel GA, Hertz L (2001) Glucose and lactate metabolism during brain activation. J Neurosci Res 66(5):824–838
Article CAS PubMed Google Scholar
Dienel GA, Wang RY, Cruz NF (2002) Generalized sensory stimulation of conscious rats increases labeling of oxidative pathways of glucose metabolism when the brain glucose-oxygen uptake ratio rises. J Cereb Blood Flow Metab 22(12):1490–1502. https://doi.org/10.1097/00004647-200212000-00009
Article CAS PubMed Google Scholar
Dienel GA, Ball KK, Cruz NF (2007a) 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. https://doi.org/10.1111/j.1471-4159.2007.04595.x
Article CAS PubMed PubMed Central Google Scholar
Dienel GA, Schmidt KC, Cruz NF (2007b) Astrocyte activation in vivo during graded photic stimulation. J Neurochem 103(4):1506–1522. https://doi.org/10.1111/j.1471-4159.2007.04859.x
Article CAS PubMed Google Scholar
Dienel GA, Behar KL, Rothman DL (2018) Cellular origin of [¹⁸F]FDG-PET imaging signals during ceftriaxone-stimulated glutamate uptake: astrocytes and neurons. Neuroscientist 24(4):316–328
Article CAS PubMed Google Scholar
DiNuzzo M (2013) Kinetic analysis of glycogen turnover: relevance to human brain ¹³C-NMR spectroscopy. J Cereb Blood Flow Metab 33(10):1540–1548. https://doi.org/10.1038/jcbfm.2013.98
Article CAS PubMed PubMed Central Google Scholar
DiNuzzo M, Mangia S, Maraviglia B, Giove F (2010a) Changes in glucose uptake rather than lactate shuttle take center stage in subserving neuroenergetics: evidence from mathematical modeling. J Cereb Blood Flow Metab 30(3):586–602. https://doi.org/10.1038/jcbfm.2009.232
Article CAS PubMed Google Scholar
DiNuzzo M, Mangia S, Maraviglia B, Giove F (2010b) 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(12):1895–1904. https://doi.org/10.1038/jcbfm.2010.151
Article CAS PubMed PubMed Central Google Scholar
DiNuzzo M, Maraviglia B, Giove F (2011) Why does the brain (not) have glycogen? BioEssays 33(5):319–326. https://doi.org/10.1002/bies.201000151
Article CAS PubMed Google Scholar
DiNuzzo M, Mangia S, Maraviglia B, Giove F (2012) The role of astrocytic glycogen in supporting the energetics of neuronal activity. Neurochem Res 37:2432–2438. https://doi.org/10.1007/s11064-012-0802-5
Article CAS PubMed PubMed Central Google Scholar
DiNuzzo M, Giove F, Maraviglia B, Mangia S (2017) Computational flux balance analysis predicts that stimulation of energy metabolism in astrocytes and their metabolic interactions with neurons depend on uptake of K⁺ rather than glutamate. Neurochem Res 42(1):202–216. https://doi.org/10.1007/s11064-016-2048-0
Article CAS PubMed Google Scholar
Dringen R, Gebhardt R, Hamprecht B (1993) Glycogen in astrocytes: possible function as lactate supply for neighboring cells. Brain Res 623(2):208–214
Article CAS PubMed Google Scholar
Dringen R, Pawlowski PG, Hirrlinger J (2005) Peroxide detoxification by brain cells. J Neurosci Res 79(1–2):157–165. https://doi.org/10.1002/jnr.20280
Article CAS PubMed Google Scholar
Dringen R, Hoepken HH, Minich T, Ruedig C (2007) Pentose phosphate pathway and NADPH metabolism. In: Gibson GE, Dienel GA (eds) Brain energetics. Integration of molecular and cellular processes. Handbook of neurochemistry and molecular neurobiology, 3rd edn. Springer, Berlin, pp 41–62
Chapter Google Scholar
Drulis-Fajdasz D, Wojtowicz T, Wawrzyniak M, Wlodarczyk J, Mozrzymas JW, Rakus D (2015) Involvement of cellular metabolism in age-related LTP modifications in rat hippocampal slices. Oncotarget 6(16):14065–14081. https://doi.org/10.18632/oncotarget.4188
Article PubMed PubMed Central Google Scholar
Drulis-Fajdasz D, Gizak A, Wojtowicz T, Wisniewski JR, Rakus D (2018) Aging-associated changes in hippocampal glycogen metabolism in mice. Evidence for and against astrocyte-to-neuron lactate shuttle. Glia 66(7):1481–1495. https://doi.org/10.1002/glia.23319
Article PubMed PubMed Central Google Scholar
Duran J, Guinovart JJ (2015) Brain glycogen in health and disease. Mol Asp Med 46:70–77. https://doi.org/10.1016/j.mam.2015.08.007
Article CAS Google Scholar
Duran J, Gruart A, Varea O, López-Soldado I, Delgado-García JM, Guinovart JJ (2019) Lack of Neuronal Glycogen Impairs Memory Formation and Learning-Dependent Synaptic Plasticity in Mice. Frontiers in Cellular Neuroscience 13
Google Scholar
Duran J, Saez I, Gruart A, Guinovart JJ, Delgado-Garcia JM (2013) 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(4):550–556. https://doi.org/10.1038/jcbfm.2012.200
Article CAS PubMed PubMed Central Google Scholar
El Hayek L, Khalifeh M, Zibara V, Abi Assaad R, Emmanuel N, Karnib N, El-Ghandour R, Nasrallah P, Bilen M, Ibrahim P, Younes J, Abou Haidar E, Barmo N, Jabre V, Stephan JS, Sleiman SF (2019) Lactate mediates the effects of exercise on learning and memory through SIRT1-dependent activation of hippocampal brain-derived Neurotrophic factor (BDNF). J Neurosci 39(13):2369–2382. https://doi.org/10.1523/jneurosci.1661-18.2019
Article CAS PubMed PubMed Central Google Scholar
Fray AE, Forsyth RJ, Boutelle MG, Fillenz M (1996) The mechanisms controlling physiologically stimulated changes in rat brain glucose and lactate: a microdialysis study. J Physiol 496(1):49–57. https://doi.org/10.1113/jphysiol.1996.sp021664
Article CAS PubMed PubMed Central Google Scholar
Gandhi GK, Cruz NF, Ball KK, Dienel GA (2009a) Astrocytes are poised for lactate trafficking and release from activated brain and for supply of glucose to neurons. J Neurochem 111(2):522–536. https://doi.org/10.1111/j.1471-4159.2009.06333.x
Article CAS PubMed PubMed Central Google Scholar
Gandhi GK, Cruz NF, Ball KK, Theus SA, Dienel GA (2009b) Selective astrocytic gap junctional trafficking of molecules involved in the glycolytic pathway: impact on cellular brain imaging. J Neurochem 110(3):857–869. https://doi.org/10.1111/j.1471-4159.2009.06173.x
Article CAS PubMed PubMed Central Google Scholar
Gao V, Suzuki A, Magistretti PJ, Lengacher S, Pollonini G, Steinman MQ, Alberini CM (2016) Astrocytic beta2-adrenergic receptors mediate hippocampal long-term memory consolidation. Proc Natl Acad Sci U S A 113(30):8526–8531. https://doi.org/10.1073/pnas.1605063113
Article CAS PubMed PubMed Central Google Scholar
Gebril HM, Avula B, Wang YH, Khan IA, Jekabsons MB (2016) (13)C metabolic flux analysis in neurons utilizing a model that accounts for hexose phosphate recycling within the pentose phosphate pathway. Neurochem Int 93:26–39. https://doi.org/10.1016/j.neuint.2015.12.008
Article CAS PubMed Google Scholar
Gibbs ME (2016) Role of glycogenolysis in memory and learning: regulation by noradrenaline, serotonin and ATP. Front Integr Neurosci 9:70. https://doi.org/10.3389/fnint.2015.00070
Article CAS PubMed PubMed Central Google Scholar
Gibbs ME, Hertz L (2005) Importance of glutamate-generating metabolic pathways for memory consolidation in chicks. J Neurosci Res 81(2):293–300. https://doi.org/10.1002/jnr.20548
Article CAS PubMed Google Scholar
Gibbs ME, Lloyd HG, Santa T, Hertz L (2007) Glycogen is a preferred glutamate precursor during learning in 1-day-old chick: biochemical and behavioral evidence. J Neurosci Res 85(15):3326–3333. https://doi.org/10.1002/jnr.21307
Article CAS PubMed Google Scholar
Gilbert E, Tang JM, Ludvig N, Bergold PJ (2006) Elevated lactate suppresses neuronal firing in vivo and inhibits glucose metabolism in hippocampal slice cultures. Brain Res 1117(1):213–223. https://doi.org/10.1016/j.brainres.2006.07.107
Article CAS PubMed Google Scholar
Griffiths JR, Dwek RA, Radda GK (1976) Heterotropic interactions of ligands with phosphorylase b. Eur J Biochem 61(1):243–251
Article CAS PubMed Google Scholar
Grossbard L, Schimke RT (1966) Multiple hexokinases of rat tissues. Purification and comparison of soluble forms. J Biol Chem 241(15):3546–3560
CAS PubMed Google Scholar
Gundersen V, Storm-Mathisen J, Bergersen LH (2015) Neuroglial Transmission. Physiol Rev 95(3):695–726. https://doi.org/10.1152/physrev.00024.2014
Article CAS PubMed Google Scholar
Halestrap AP (1975) The mitochondrial pyruvate carrier. Kinetics and specificity for substrates and inhibitors. Biochem J 148(1):85–96
Article CAS PubMed PubMed Central Google Scholar
Halestrap AP, Denton RM (1975) The specificity and metabolic implications of the inhibition of pyruvate transport in isolated mitochondria and intact tissue preparations by alpha-Cyano-4-hydroxycinnamate and related compounds. Biochem J 148(1):97–106
Article CAS PubMed PubMed Central Google Scholar
Halestrap AP, Price NT (1999) The proton-linked monocarboxylate transporter (MCT) family: structure, function and regulation. Biochem J 343(Pt 2):281–299
Article CAS PubMed PubMed Central Google Scholar
van Hall G, Stromstad M, Rasmussen P, Jans O, Zaar M, Gam C, Quistorff B, Secher NH, Nielsen HB (2009) Blood lactate is an important energy source for the human brain. J Cereb Blood Flow Metab 29(6):1121–1129. https://doi.org/10.1038/jcbfm.2009.35
Article CAS PubMed Google Scholar
Hertz L, Chen Y (2017) Integration between glycolysis and glutamate-glutamine cycle flux may explain preferential glycolytic increase during brain activation, requiring glutamate. Front Integr Neurosci 11:18. https://doi.org/10.3389/fnint.2017.00018
Article CAS PubMed PubMed Central Google Scholar
Hertz L, Dienel GA (2005) Lactate transport and transporters: general principles and functional roles in brain cells. J Neurosci Res 79(1–2):11–18. https://doi.org/10.1002/jnr.20294
Article CAS PubMed Google Scholar
Hertz L, Gibbs ME (2009) What learning in day-old chickens can teach a neurochemist: focus on astrocyte metabolism. J Neurochem 109(Suppl 1):10–16. https://doi.org/10.1111/j.1471-4159.2009.05939.x
Article CAS PubMed Google Scholar
Hertz L, Rothman DL (2017) Glutamine-glutamate cycle flux is similar in cultured astrocytes and brain and both glutamate production and oxidation are mainly catalyzed by aspartate aminotransferase. Biology (Basel) 6(1):17. https://doi.org/10.3390/biology6010017
Article Google Scholar
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. https://doi.org/10.1038/sj.jcbfm.9600343
Article CAS PubMed Google Scholar
Hertz L, Gerkau NJ, Xu J, Durry S, Song D, Rose CR, Peng L (2015a) Roles of astrocytic Na(+),K(+)-ATPase and glycogenolysis for K(+) homeostasis in mammalian brain. J Neurosci Res 93(7):1019–1030. https://doi.org/10.1002/jnr.23499
Article CAS PubMed Google Scholar
Hertz L, Xu J, Song D, Du T, Li B, Yan E, Peng L (2015b) Astrocytic glycogenolysis: mechanisms and functions. Metab Brain Dis 30(1):317–333. https://doi.org/10.1007/s11011-014-9536-1
Article CAS PubMed Google Scholar
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. https://doi.org/10.1210/en.2007-1252
Article CAS PubMed PubMed Central Google Scholar
Hildebrand A, Lormes W, Emmert J, Liu Y, Lehmann M, Steinacker JM (2000) Lactate concentration in plasma and red blood cells during incremental exercise. Int J Sports Med 21(07):463–468. https://doi.org/10.1055/s-2000-7412
Article CAS PubMed Google Scholar
Hof PR, Pascale E, Magistretti PJ (1988) K⁺ at concentrations reached in the extracellular space during neuronal activity promotes a Ca²⁺-dependent glycogen hydrolysis in mouse cerebral cortex. J Neurosci 8(6):1922–1928
Article CAS PubMed PubMed Central Google Scholar
Holden JE, Mori K, Dienel GA, Cruz NF, Nelson T, Sokoloff L (1991) Modeling the dependence of hexose distribution volumes in brain on plasma glucose concentration: implications for estimation of the local 2-deoxyglucose lumped constant. J Cereb Blood Flow Metab 11(2):171–182. https://doi.org/10.1038/jcbfm.1991.50
Article CAS PubMed Google Scholar
Hudson JW, Golding GB, Crerar MM (1993) Evolution of allosteric control in glycogen phosphorylase. J Mol Biol 234(3):700–721. https://doi.org/10.1006/jmbi.1993.1621
Article CAS PubMed Google Scholar
Jackson JG, Robinson MB (2018) Regulation of mitochondrial dynamics in astrocytes: mechanisms, consequences, and unknowns. Glia 66(6):1213–1234. https://doi.org/10.1002/glia.23252
Article PubMed Google Scholar
Jakobsen E, Bak LK, Walls AB, Reuschlein AK, Schousboe A, Waagepetersen HS (2017) Glycogen shunt activity and glycolytic supercompensation in astrocytes may be distinctly mediated via the muscle form of glycogen phosphorylase. Neurochem Res 42(9):2490–2494. https://doi.org/10.1007/s11064-017-2267-z
Article CAS PubMed Google Scholar
Jang S, Nelson Jessica C, Bend Eric G, Rodríguez-Laureano L, Tueros Felipe G, Cartagenova L, Underwood K, Jorgensen Erik M, Colón-Ramos Daniel A (2016) Glycolytic enzymes localize to synapses under energy stress to support synaptic function. Neuron 90(2):278–291. https://doi.org/10.1016/j.neuron.2016.03.011
Article CAS PubMed PubMed Central Google Scholar
Jekabsons MB, Gebril HM, Wang YH, Avula B, Khan IA (2017) Updates to a 13C metabolic flux analysis model for evaluating energy metabolism in cultured cerebellar granule neurons from neonatal rats. Neurochem Int 109:54–67. https://doi.org/10.1016/j.neuint.2017.03.020
Article CAS PubMed PubMed Central Google Scholar
Kong J, Shepel PN, Holden CP, Mackiewicz M, Pack AI, Geiger JD (2002) Brain glycogen decreases with increased periods of wakefulness: implications for homeostatic drive to sleep. J Neurosci 22(13):5581–5587
Article CAS PubMed PubMed Central Google Scholar
Lanz B, Gruetter R, Duarte JM (2013) Metabolic flux and compartmentation analysis in the brain in vivo. Front Endocrinol (Lausanne) 4:156. https://doi.org/10.3389/fendo.2013.00156
Article Google Scholar
Lauritzen KH, Morland C, Puchades M, Holm-Hansen S, Hagelin EM, Lauritzen F, Attramadal H, Storm-Mathisen J, Gjedde A, Bergersen LH (2014) Lactate receptor sites link neurotransmission, neurovascular coupling, and brain energy metabolism. Cereb Cortex 24(10):2784–2795. https://doi.org/10.1093/cercor/bht136
Article PubMed Google Scholar
Lavialle M, Aumann G, Anlauf E, Prols F, Arpin M, Derouiche A (2011) Structural plasticity of perisynaptic astrocyte processes involves ezrin and metabotropic glutamate receptors. Proc Natl Acad Sci U S A 108(31):12915–12919. https://doi.org/10.1073/pnas.1100957108
Article PubMed PubMed Central Google Scholar
Lowry OH, Passonneau JV (1964) The relationships between substrates and enzymes of glycolysis in brain. J Biol Chem 239:31–42
CAS PubMed Google Scholar
Madsen PL, Linde R, Hasselbalch SG, Paulson OB, Lassen NA (1998) Activation-induced resetting of cerebral oxygen and glucose uptake in the rat. J Cereb Blood Flow Metab 18(7):742–748. https://doi.org/10.1097/00004647-199807000-00005
Article CAS PubMed Google Scholar
Madsen PL, Cruz NF, Sokoloff L, Dienel GA (1999) Cerebral oxygen/glucose ratio is low during sensory stimulation and rises above normal during recovery: excess glucose consumption during stimulation is not accounted for by lactate efflux from or accumulation in brain tissue. J Cereb Blood Flow Metab 19(4):393–400. https://doi.org/10.1097/00004647-199904000-00005
Article CAS PubMed Google Scholar
Magistretti PJ, Pellerin L (1996) Cellular mechanisms of brain energy metabolism. Relevance to functional brain imaging and to neurodegenerative disorders. Ann N Y Acad Sci 777:380–387
Article CAS PubMed Google Scholar
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. https://doi.org/10.1111/j.1471-4159.2009.06003.x
Article CAS PubMed PubMed Central Google Scholar
Mangia S, DiNuzzo M, Giove F, Carruthers A, Simpson IA, Vannucci SJ (2011) Response to ‘comment on recent modeling studies of astrocyte-neuron metabolic interactions’: much ado about nothing. J Cereb Blood Flow Metab 31(6):1346–1353. https://doi.org/10.1038/jcbfm.2011.29
Article CAS PubMed PubMed Central Google Scholar
Manning Fox JE, Meredith D, Halestrap AP (2000) Characterisation of human monocarboxylate transporter 4 substantiates its role in lactic acid efflux from skeletal muscle. J Physiol 529(Pt 2):285–293
CAS PubMed PubMed Central Google Scholar
Matsui T, Soya S, Okamoto M, Ichitani Y, Kawanaka K, Soya H (2011) Brain glycogen decreases during prolonged exercise. J Physiol 589(Pt 13):3383–3393. https://doi.org/10.1113/jphysiol.2010.203570
Article CAS PubMed PubMed Central Google Scholar
Matsui T, Ishikawa T, Ito H, Okamoto M, Inoue K, Lee MC, Fujikawa T, Ichitani Y, Kawanaka K, Soya H (2012) Brain glycogen supercompensation following exhaustive exercise. J Physiol 590(3):607–616. https://doi.org/10.1113/jphysiol.2011.217919
Article CAS PubMed Google Scholar
Matsui T, Omuro H, Liu YF, Soya M, Shima T, McEwen BS, Soya H (2017) Astrocytic glycogen-derived lactate fuels the brain during exhaustive exercise to maintain endurance capacity. Proc Natl Acad Sci U S A 114(24):6358–6363. https://doi.org/10.1073/pnas.1702739114
Article CAS PubMed PubMed Central Google Scholar
Mayer D, Seelmann-Eggebert G, Letsch I (1992) Glycogen phosphorylase isoenzymes from hepatoma 3924A and from a non-tumorigenic liver cell line. Comparison with the liver and brain enzymes. Biochem J 282(Pt 3):665–673
Article CAS PubMed PubMed Central Google Scholar
McKenna MC, Sonnewald U, Huang X, Stevenson J, Zielke HR (1996) Exogenous glutamate concentration regulates the metabolic fate of glutamate in astrocytes. J Neurochem 66(1):386–393
Article CAS PubMed Google Scholar
McKenna MC, Hopkins IB, Carey A (2001) Alpha-cyano-4-hydroxycinnamate decreases both glucose and lactate metabolism in neurons and astrocytes: implications for lactate as an energy substrate for neurons. J Neurosci Res 66(5):747–754
Article CAS PubMed Google Scholar
Morgan HE, Parmeggiani A (1964) Regulation of glycogenollysis in muscle. 3. Control of muscle glycogen phosphorylase activity. J Biol Chem 239:2440–2445
CAS PubMed Google Scholar
Moussawi K, Riegel A, Nair S, Kalivas PW (2011) Extracellular glutamate: functional compartments operate in different concentration ranges. Front Syst Neurosci 5:94. https://doi.org/10.3389/fnsys.2011.00094
Article CAS PubMed PubMed Central Google Scholar
Mozrzymas J, Szczęsny T, Rakus D (2011) The effect of glycogen phosphorolysis on basal glutaminergic transmission. Biochem Biophys Res Commun 404(2):652–655. https://doi.org/10.1016/j.bbrc.2010.12.033
Article CAS PubMed Google Scholar
Müller MS, Fox R, Schousboe A, Waagepetersen HS, Bak LK (2014) Astrocyte glycogenolysis is triggered by store-operated calcium entry and provides metabolic energy for cellular calcium homeostasis. Glia 62(4):526–534. https://doi.org/10.1002/glia.22623
Article PubMed Google Scholar
Müller MS, Pedersen SE, Walls AB, Waagepetersen HS, Bak LK (2015) Isoform-selective regulation of glycogen phosphorylase by energy deprivation and phosphorylation in astrocytes. Glia 63(1):154–162. https://doi.org/10.1002/glia.22741
Article PubMed Google Scholar
Nadeau OW, Fontes JD, Carlson GM (2018) The regulation of glycogenolysis in the brain. J Biol Chem 293(19):7087–7088. https://doi.org/10.1074/jbc.R117.803023
Article Google Scholar
Nakao Y, Gotoh J, Kuang TY, Cohen DM, Pettigrew KD, Sokoloff L (1999) Cerebral blood flow responses to somatosensory stimulation are unaffected by scopolamine in unanesthetized rat. J Pharmacol Exp Ther 290(2):929–934
CAS PubMed Google Scholar
Nakao Y, Itoh Y, Kuang TY, Cook M, Jehle J, Sokoloff L (2001) Effects of anesthesia on functional activation of cerebral blood flow and metabolism. Proc Natl Acad Sci U S A 98(13):7593–7598. https://doi.org/10.1073/pnas.121179898
Article CAS PubMed PubMed Central Google Scholar
Nasrallah FA, Garner B, Ball GE, Rae C (2008) Modulation of brain metabolism by very low concentrations of the commonly used drug delivery vehicle dimethyl sulfoxide (DMSO). J Neurosci Res 86(1):208–214. https://doi.org/10.1002/jnr.21477
Article CAS PubMed Google Scholar
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. https://doi.org/10.1097/01.wcb.0000128533.84196.d8
Article CAS PubMed Google Scholar
Newman LA, Korol DL, Gold PE (2011) Lactate produced by glycogenolysis in astrocytes regulates memory processing. PLoS One 6(12):e28427. https://doi.org/10.1371/journal.pone.0028427
Article CAS PubMed PubMed Central Google Scholar
Newsholme EA, Rolleston FS, Taylor K (1968) Factors affecting the glucose 6-phosphate inhibition of hexokinase from cerebral cortex tissue of the guinea pig. Biochem J 106(1):193–201
CAS PubMed PubMed Central Google Scholar
Obel LF, Müller MS, Walls AB, Sickmann HM, Bak LK, Waagepetersen HS, Schousboe A (2012) Brain glycogen-new perspectives on its metabolic function and regulation at the subcellular level. Front Neuroenerg 4:3. https://doi.org/10.3389/fnene.2012.00003
Article CAS Google Scholar
Oe Y, Baba O, Ashida H, Nakamura KC, Hirase H (2016) Glycogen distribution in the microwave-fixed mouse brain reveals heterogeneous astrocytic patterns. Glia 64(9):1532–1545. https://doi.org/10.1002/glia.23020
Article PubMed PubMed Central Google Scholar
Ottersen OP, Zhang N, Walberg F (1992) Metabolic compartmentation of glutamate and glutamine: morphological evidence obtained by quantitative immunocytochemistry in rat cerebellum. Neuroscience 46(3):519–534
Article CAS PubMed Google Scholar
Öz G, DiNuzzo M, Kumar A, Moheet A, Seaquist ER (2015) Revisiting glycogen content in the human brain. Neurochem Res 40(12):2473–2481. https://doi.org/10.1007/s11064-015-1664-4
Article CAS PubMed PubMed Central Google Scholar
Öz G, DiNuzzo M, Kumar A, Moheet A, Khowaja A, Kubisiak K, Eberly LE, Seaquist ER (2017) Cerebral glycogen in humans following acute and recurrent hypoglycemia: Implications on a role in hypoglycemia unawareness. J Cereb Blood Flow Metab 37(8):2883–2893. https://doi.org/10.1177/0271678x16678240
Article CAS PubMed Google Scholar
Parpura V, Basarsky TA, Liu F, Jeftinija K, Jeftinija S, Haydon PG (1994) Glutamate-mediated astrocyte-neuron signalling. Nature 369(6483):744–747
Article CAS PubMed Google Scholar
Pearson-Leary J, McNay EC (2016) Novel roles for the insulin-regulated glucose transporter-4 in hippocampally dependent memory. J Neurosci 36(47):11851–11864. https://doi.org/10.1523/jneurosci.1700-16.2016
Article CAS PubMed PubMed Central Google Scholar
Pearson-Leary J, Jahagirdar V, Sage J, McNay EC (2018) Insulin modulates hippocampally-mediated spatial working memory via glucose transporter-4. Behav Brain Res 338:32–39. https://doi.org/10.1016/j.bbr.2017.09.033
Article CAS PubMed Google Scholar
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
Article CAS PubMed PubMed Central Google Scholar
Pfeiffer-Guglielmi B, Bröer S, Bröer A, Hamprecht B (2000) Isozyme pattern of glycogen phosphorylase in the rat nervous system and rat astroglia-rich primary cultures: electrophoretic and polymerase chain reaction studies. Neurochem Res 25(11):1485–1491
Article CAS PubMed Google Scholar
Pfeiffer-Guglielmi B, Fleckenstein B, Jung G, Hamprecht B (2003) Immunocytochemical localization of glycogen phosphorylase isozymes in rat nervous tissues by using isozyme-specific antibodies. J Neurochem 85(1):73–81
Article CAS PubMed Google Scholar
Prebil M, Vardjan N, Jensen J, Zorec R, Kreft M (2011) Dynamic monitoring of cytosolic glucose in single astrocytes. Glia 59(6):903–913. https://doi.org/10.1002/glia.21161
Article PubMed Google Scholar
Preller A, Wilson JE (1992) Localization of the type III isozyme of hexokinase at the nuclear periphery. Arch Biochem Biophys 294(2):482–492
Article CAS PubMed Google Scholar
Price TB, Taylor R, Mason GF, Rothman DL, Shulman GI, Shulman RG (1994) Turnover of human muscle glycogen with low-intensity exercise. Med Sci Sports Exerc 26(8):983–991
Article CAS PubMed Google Scholar
Quistorff B, Secher NH, Van Lieshout JJ (2008) Lactate fuels the human brain during exercise. FASEB J 22(10):3443–3449. https://doi.org/10.1096/fj.08-106104
Article CAS PubMed Google Scholar
Rahman B, Kussmaul L, Hamprecht B, Dringen R (2000) Glycogen is mobilized during the disposal of peroxides by cultured astroglial cells from rat brain. Neurosci Lett 290(3):169–172
Article CAS PubMed Google Scholar
Reichenbach A, Derouiche A, Kirchhoff F (2010) Morphology and dynamics of perisynaptic glia. Brain Res Rev 63(1–2):11–25. https://doi.org/10.1016/j.brainresrev.2010.02.003
Article PubMed Google Scholar
Reivich M, Kuhl D, Wolf A, Greenberg J, Phelps M, Ido T, Casella V, Fowler J, Hoffman E, Alavi A, Som P, Sokoloff L (1979) The [18F]fluorodeoxyglucose method for the measurement of local cerebral glucose utilization in man. Circ Res 44(1):127–137
Article CAS PubMed Google Scholar
Rothman DL, Dienel GA (2019) Development of a model to test whether glycogenolysis can support astrocytic energy demands of Na+,K+-ATPase and glutamate-glutamine cycling, sparing an equivalent amount of glucose for neurons. in M. DiNuzzo, A. Schousboe (eds.), Brain Glycogen Metabolism, Advances in Neurobiology 23. https://doi.org/10.1007/978-3-030-27480-1_1
Saez I, Duran J, Sinadinos C, Beltran A, Yanes O, Tevy MF, Martínez-Pons C, Milán M, Guinovart JJ (2014) Neurons have an active glycogen metabolism that contributes to tolerance to hypoxia. J Cereb Blood Flow Metab 34(6):945–955. https://doi.org/10.1038/jcbfm.2014.33
Article CAS PubMed PubMed Central Google Scholar
Scanziani M, Salin PA, Vogt KE, Malenka RC, Nicoll RA (1997) Use-dependent increases in glutamate concentration activate presynaptic metabotropic glutamate receptors. Nature 385(6617):630–634. https://doi.org/10.1038/385630a0
Article CAS PubMed Google Scholar
Sebastian S, White JA, Wilson JE (1999) Characterization of the rat type III hexokinase gene promoter. A functional octamer 1 motif is critical for basal promoter activity. J Biol Chem 274(44):31700–31706
Article CAS PubMed Google Scholar
Shulman RG, Rothman DL (2001) The “glycogen shunt” in exercising muscle: a role for glycogen in muscle energetics and fatigue. Proc Natl Acad Sci U S A 98(2):457–461. https://doi.org/10.1073/pnas.98.2.457
Article CAS PubMed PubMed Central Google Scholar
Shulman RG, Hyder F, Rothman DL (2001) Cerebral energetics and the glycogen shunt: neurochemical basis of functional imaging. Proc Natl Acad Sci U S A 98(11):6417–6422. https://doi.org/10.1073/pnas.101129298
Article CAS PubMed PubMed Central Google Scholar
Sickmann HM, Walls AB, Schousboe A, Bouman SD, Waagepetersen HS (2009) Functional significance of brain glycogen in sustaining glutamatergic neurotransmission. J Neurochem 109(Suppl 1):80–86. https://doi.org/10.1111/j.1471-4159.2009.05915.x
Article CAS PubMed Google Scholar
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. https://doi.org/10.1038/sj.jcbfm.9600521
Article CAS PubMed Google Scholar
Sokoloff L, Reivich M, Kennedy C, Des Rosiers MH, Patlak CS, Pettigrew KD, Sakurada O, Shinohara M (1977) The [¹⁴C]deoxyglucose method for the measurement of local cerebral glucose utilization: theory, procedure, and normal values in the conscious and anesthetized albino rat. J Neurochem 28(5):897–916
Article CAS PubMed Google Scholar
Steinman MQ, Gao V, Alberini CM (2016) The role of lactate-mediated metabolic coupling between astrocytes and neurons in long-term memory formation. Front Integr Neurosci 10:10. https://doi.org/10.3389/fnint.2016.00010
Article PubMed PubMed Central Google Scholar
Storm-Mathisen J, Leknes AK, Bore AT, Vaaland JL, Edminson P, Haug FM, Ottersen OP (1983) First visualization of glutamate and GABA in neurones by immunocytochemistry. Nature 301(5900):517–520
Article CAS PubMed Google Scholar
Suda S, Shinohara M, Miyaoka M, Lucignani G, Kennedy C, Sokoloff L (1990) The lumped constant of the deoxyglucose method in hypoglycemia: effects of moderate hypoglycemia on local cerebral glucose utilization in the rat. J Cereb Blood Flow Metab 10(4):499–509. https://doi.org/10.1038/jcbfm.1990.92
Article CAS PubMed Google Scholar
Suh SW, Bergher JP, Anderson CM, Treadway JL, Fosgerau K, Swanson RA (2007) Astrocyte glycogen sustains neuronal activity during hypoglycemia: studies with the glycogen phosphorylase inhibitor CP-316,819 ([R-R∗,S∗]-5-chloro-N-[2-hydroxy-3-(methoxymethylamino)-3-oxo-1-(phenylmethyl)pro pyl]-1H-indole-2-carboxamide). J Pharmacol Exp Ther 321(1):45–50. https://doi.org/10.1124/jpet.106.115550
Article CAS PubMed Google Scholar
Suzuki A, Stern SA, Bozdagi O, Huntley GW, Walker RH, Magistretti PJ, Alberini CM (2011) Astrocyte-neuron lactate transport is required for long-term memory formation. Cell 144(5):810–823. https://doi.org/10.1016/j.cell.2011.02.018
Article CAS PubMed PubMed Central Google Scholar
Ueda T (2016) Vesicular glutamate uptake. Adv Neurobiol 13:173–221. https://doi.org/10.1007/978-3-319-45096-4_7
Article PubMed Google Scholar
Veech RL, Harris RL, Veloso D, Veech EH (1973) Freeze-blowing: a new technique for the study of brain in vivo. J Neurochem 20(1):183–188
Article CAS PubMed Google Scholar
Vissing J, Andersen M, Diemer NH (1996) Exercise-induced changes in local cerebral glucose utilization in the rat. J Cereb Blood Flow Metab 16(4):729–736. https://doi.org/10.1097/00004647-199607000-00025
Article CAS PubMed Google Scholar
Waagepetersen HS, Sonnewald U, Larsson OM, Schousboe A (2000) A possible role of alanine for ammonia transfer between astrocytes and glutamatergic neurons. J Neurochem 75(2):471–479
Article CAS PubMed Google Scholar
Walls AB, Sickmann HM, Brown A, Bouman SD, Ransom B, Schousboe A, Waagepetersen HS (2008) Characterization of 1,4-dideoxy-1,4-imino-d-arabinitol (DAB) as an inhibitor of brain glycogen shunt activity. J Neurochem 105(4):1462–1470. https://doi.org/10.1111/j.1471-4159.2008.05250.x
Article CAS PubMed Google Scholar
Watanabe H, Passonneau JV (1973) Factors affecting the turnover of cerebral glycogen and limit dextrin in vivo. J Neurochem 20(6):1543–1554
Article CAS PubMed Google Scholar
Wilhelm F, Hirrlinger J (2011) The NAD+/NADH redox state in astrocytes: Independent control of the NAD+ and NADH content. J Neurosci Res 89(12):1956–1964. https://doi.org/10.1002/jnr.22638
Article CAS PubMed Google Scholar
Wilson JE (2003) Isozymes of mammalian hexokinase: structure, subcellular localization and metabolic function. J Exp Biol 206(Pt 12):2049–2057
Article CAS PubMed Google Scholar
Xu J, Song D, Xue Z, Gu L, Hertz L, Peng L (2013) Requirement of glycogenolysis for uptake of increased extracellular K+ in astrocytes: potential implications for K+ homeostasis and glycogen usage in brain. Neurochem Res 38(3):472–485. https://doi.org/10.1007/s11064-012-0938-3
Article CAS PubMed Google Scholar
Xu J, Song D, Bai Q, Zhou L, Cai L, Hertz L, Peng L (2014) Role of glycogenolysis in stimulation of ATP release from cultured mouse astrocytes by transmitters and high K+ concentrations. ASN Neuro 6(1):e00132. https://doi.org/10.1042/an20130040
Article PubMed PubMed Central Google Scholar
Yang J, Ruchti E, Petit J-M, Jourdain P, Grenningloh G, Allaman I, Magistretti PJ (2014) Lactate promotes plasticity gene expression by potentiating NMDA signaling in neurons. Proc Natl Acad Sci U S A 111(33):12228–12233. https://doi.org/10.1073/pnas.1322912111
Article CAS PubMed PubMed Central Google Scholar
Yellen G (2018) Fueling thought: management of glycolysis and oxidative phosphorylation in neuronal metabolism. J Cell Biol 217(7):2235–2246. https://doi.org/10.1083/jcb.201803152
Article CAS PubMed PubMed Central Google Scholar
Yu Y, Herman P, Rothman DL, Agarwal D, Hyder F (2018) Evaluating the gray and white matter energy budgets of human brain function. J Cereb Blood Flow Metab 38(8):0339–1353. https://doi.org/10.1177/0271678x17708691
Article Google Scholar
Zhang Y, Xue Y, Meng S, Luo Y, Liang J, Li J, Ai S, Sun C, Shen H, Zhu W, Wu P, Lu L, Shi J (2016) Inhibition of lactate transport erases drug memory and prevents drug relapse. Biol Psychiatry 79(11):928–929. https://doi.org/10.1016/j.biopsych.2015.07.007
Article CAS PubMed Google Scholar
Zimmer ER, Parent MJ, Souza DG, Leuzy A, Lecrux C, Kim HI, Gauthier S, Pellerin L, Hamel E, Rosa-Neto P (2017) [¹⁸F]FDG PET signal is driven by astroglial glutamate transport. Nat Neurosci 20(3):393–395. https://doi.org/10.1038/nn.4492
Article CAS PubMed PubMed Central Google Scholar
Zorec R, Araque A, Carmignoto G, Haydon PG, Verkhratsky A, Parpura V (2012) Astroglial excitability and gliotransmission: an appraisal of Ca2+ as a signalling route. ASN Neuro 4(2):e00080. https://doi.org/10.1042/an20110061
Article PubMed PubMed Central Google Scholar

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Conflict of interest: The authors declare that they have no conflicts of interest.

Sources of funding: DLR: R01MH109159, R01 NS087568, R01 NS100106.

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Department of Neurology, University of Arkansas for Medical Sciences, Little Rock, AR, USA
Gerald A. Dienel
Department of Cell Biology and Physiology, University of New Mexico, Albuquerque, NM, USA
Gerald A. Dienel
Magnetic Resonance Research Center and Department of Diagnostic Radiology, Yale University, New Haven, CT, USA
Douglas L. Rothman

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Center for Basic and Translational Neuroscience, University of Copenhagen, Copenhagen, Denmark
Mauro DiNuzzo
Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
Arne Schousboe

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Dienel, G.A., Rothman, D.L. (2019). Glycogenolysis in Cerebral Cortex During Sensory Stimulation, Acute Hypoglycemia, and Exercise: Impact on Astrocytic Energetics, Aerobic Glycolysis, and Astrocyte-Neuron Interactions. In: DiNuzzo, M., Schousboe, A. (eds) Brain Glycogen Metabolism. Advances in Neurobiology, vol 23. Springer, Cham. https://doi.org/10.1007/978-3-030-27480-1_8

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