Skip to main content

Advertisement

SpringerLink
Log in

Functional Importance of the Astrocytic Glycogen-Shunt and Glycolysis for Maintenance of an Intact Intra/Extracellular Glutamate Gradient

  • Published:
Neurotoxicity Research Aims and scope Submit manuscript

Abstract

It has been proposed that a considerable fraction of glucose metabolism proceeds via the glycogen-shunt consisting of conversion of glucose units to glycogen residues and subsequent production of glucose-1-phosphate to be metabolized in glycolysis after conversion to glucose-6-phosphate. The importance of this as well as the significance of ATP formed in glycolysis versus that formed by the concerted action of the tricarboxylic acid (TCA) cycle processes and oxidative phosphorylation for maintenance of glutamate transport capacity in astrocytes is discussed. It is argued that glycolytically derived energy in the form of ATP may be of particular functional importance in this context.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  • Attwell D, Laughlin SB (2001) An energy budget for signalling in the grey matter of the brain. J Cereb Blood Flow Metab 21:1133–1145

    Article  CAS  PubMed  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 26:1285–1297

    Article  CAS  PubMed  Google Scholar 

  • Brown AM, Tekkok SB, Ransom BR (2003) Glycogen regulation and functional role in mouse white matter. J Physiol 549:501–512

    Article  CAS  PubMed  Google Scholar 

  • Brown AM, Sickmann HM, Fosgerau K, Lund TM, Schousboe A, Waagepetersen HS, Ransom BR (2005) Astrocyte glycogen metabolism is required for neural activity during aglycemia or intense stimulation in mouse white matter. J Neurosci Res 79:74–80

    Article  CAS  PubMed  Google Scholar 

  • Camacho A, Montiel T, Massieu L (2006) The anion channel blocker, 4,4′-dinitrostilbene-2,2′-disulfonic acid prevents neuronal death and excitatory amino acid release during glycolysis inhibition in the hippocampus in vivo. J Neurochem 72:1005–1017

    Google Scholar 

  • Cataldo AM, Broadwell RD (1986) Cytochemical identification of cerebral glycogen and glucose-6-phosphate activity under normal and experimental conditions. II. Choroid lexus and ependymal epithelia and pericytes. J Neurocytol 15:511–524

    Article  CAS  PubMed  Google Scholar 

  • Cholet N, Pellerin L, Magistretti PJ, Hamel E (2002) Similar perisynaptic glial localization for the Na+, K+-ATPase α2 subunit and the glutamate transporters GLAST and GLT-1 in the rat somatosensory cortex. Cereb Cortex 12:515–525

    Article  CAS  PubMed  Google Scholar 

  • Chowdhury GM, Patel AB, Mason GF, Rothman DL, Behar KL (2007) Glutamatergic and GABAergic neurotransmitter cycling and energy metabolism in rat cerebral cortex during postnatal development. J Cereb Blood Flow Metab 27:1895–1907

    Article  CAS  PubMed  Google Scholar 

  • Danbolt NC (2001) Glutamate uptake. Prog Neurobiol 65:1–105

    Article  CAS  PubMed  Google Scholar 

  • 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 102:466–478

    Article  CAS  PubMed  Google Scholar 

  • Drejer J, Honoré T, Schousboe A (1987) Excitatory amino acid induced release of 3H-GABA from cultured mouse cerebral cortex interneurons. J Neurosci 7:2910–2916

    CAS  PubMed  Google Scholar 

  • Gandhi GK, Cruz NF, Ball KK, Dienel GA (2009) Astrocytes are poised for lactate trafficking and release from activated brain and for supply of glucose to neurons. J Neurochem 111:522–536

    Article  CAS  PubMed  Google Scholar 

  • Gegelashvili G, Schousboe A (1997) High-affinity glutamate transporters regulation of expression and activity. Mol Pharmacol 52:6–15

    CAS  PubMed  Google Scholar 

  • Hassel B, Westergaard N, Schousboe A, Fonnum F (1995) Metabolic differences between neurons and astrocytes from cerebral cortex and cerebellum. Neurochem Res 20:413–420

    Article  CAS  PubMed  Google Scholar 

  • Heald PJ (1953) The effect of metabolic inhibitors on respiration and glycolysis in electrically stimulated cerebral cortex slices. Biochemistry 55:625–631

    CAS  Google Scholar 

  • Hertz L, Zielke HR (2004) Astrocytic control of glutamatergic activity astrocytes as stars of the show. Trends Neurosci 27:735–743

    Article  CAS  PubMed  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 27:219–249

    Article  CAS  PubMed  Google Scholar 

  • Hyder F, Patel AB, Gjedde A, Rothman DL, Behar KL, Shulman RG (2006) Neuronal-glial glucose oxidation and glutamatergic-GABAergic function. J Cereb Blood Flow Metab 26:865–877

    Article  CAS  PubMed  Google Scholar 

  • 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 278:5929–5940

    Article  CAS  PubMed  Google Scholar 

  • Levy LM, Warr O, Attwell D (1998) Stoichiometry of the glial glutamate transporter GLT-expressed inducibly in a Chinese hamster ovary cell line selected for low endogenous Na+-dependent glutamate uptake. J Neurosci 18:9620–9628

    CAS  PubMed  Google Scholar 

  • Lovatt D, Sonnewald U, Waagepetersen HS, Schousboe A, He W, Lin JH, Han X, Takano T, Wang S, Sim FJ, Goldman SA, Nedergaard M (2007) The transcriptome and metabolic gene signature of protoplasmic astrocytes in the adult murine cortex. J Neurosci 27:12255–12266

    Article  CAS  PubMed  Google Scholar 

  • McKenna M, Gruetter R, Sonnewald U, Waagepetersen HS, Schousboe A (2006a) Energy metabolism of the brain. In: Siegel G, Brady S, Albers RW, Price A (eds) Basic neurochemistry. Elsevier Academic Press, London, pp 531–557

    Google Scholar 

  • 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 71:306–399

    Article  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 USA 91:10625–10629

    Article  CAS  PubMed  Google Scholar 

  • Pellerin L, Bouzier-Sore AK, Aubert A, Serres S, Merle M, Costalat R, Magistretti PJ (2007) Activity-dependent regulation of energy metabolism by astrocytes an update. Glia 55:1251–1262

    Article  PubMed  Google Scholar 

  • Ransom BR, Fern R (1997) Does astrocytic glycogen benefit axon function and survival in CNS white matter during glucose deprivation? Glia 21:134–141

    Article  CAS  PubMed  Google Scholar 

  • Riera JJ, Schousboe A, Waagepetersen HS, Howarth C, Hyder F (2008) The micro-architecture of the cerebral cortex functional neuroimaging models and metabolism. Neuroimage 40:1436–1459

    Article  PubMed  Google Scholar 

  • Sánchez-Carbente MR, Massieu L (1999) Transient inhibition of glutamate uptake in vivo induces neurodegeneration when energy metabolism is impaired. J Neurochem 72:129–138

    Article  PubMed  Google Scholar 

  • Sandberg M, Nyström B, Hamberger A (1985) Metabolically derived aspartate–elevated extracellular levels in vivo in iodoacetate poisoning. J Neurosci Res 13:489–495

    Article  CAS  PubMed  Google Scholar 

  • Schousboe A, Waagepetersen HS (2005) Role of astrocytes in glutamate homeostasis. Implications for excitotoxicity. Neurotox Res 8:221–225

    Article  CAS  PubMed  Google Scholar 

  • Schousboe A, Sickmann HM, Bak LK, Schousboe I, Bouman SD, Waagepetersen HS (2009) A functioning glycolysis is important for maintenance of glutamate transport in cultured astrocytes. J Neurochem 109(Suppl. 1):288–289

    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 USA 98:457–461

    Article  CAS  PubMed  Google Scholar 

  • Shulman RG, Hyder F, Rothman DL (2001) Cerebral energetics and the glycogen shunt neurochemical basis of functional imaging. Proc Natl Acad Sci USA 98:6417–6422

    Article  CAS  PubMed  Google Scholar 

  • Sickmann HM (2009) Glutamatergic neurotransmission under physiological and diabetic conditions—involvement of brain glycogen. Ph.D. thesis, University of Copenhagen, pp 1–81

  • 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

    Article  CAS  PubMed  Google Scholar 

  • Suh SW, Bergher JP, Anderson CM, Treadway JL, Fosgerau K, Swanson RA (2007) Astrocyte glycogen sustains neuronal activity during hypoglycaemia. Studies with the glycogen phosphorylase inhibitor CP-316, 819 ([R-R*, S*]-5-chloro-N-[2-hydroxy-3-(methoxymethylamino)-3-oxo-1-(phenylmethyl)propyl]-1H-indole-2-carboxamide). J Pharmacol Exp Ther 321:45–50

    Article  CAS  PubMed  Google Scholar 

  • Swanson RA (1992) Physiologic coupling of glial glycogen metabolism to neuronal activity in brain. Can J Physiol Pharmacol 70(Suppl):S138–S144

    CAS  PubMed  Google Scholar 

  • Swanson RA, Choi DW (1993) Glial glycogen stores affect neuronal survival during glucose deprivation in vitro. J Cereb Blood Flow Metab 13:162–169

    CAS  PubMed  Google Scholar 

  • Waagepetersen HS, Sonnewald U, Schousboe A (2009) Energy and amino acid neurotransmitter metabolism in astrocytes. In: Parpura V, Haydon PG (eds) Astrocytes in (Patho)physiology of the nervous system. Springer, Boston, MA, pp 177–199

    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 105:1462–1470

    Article  CAS  PubMed  Google Scholar 

  • Walls AB, Heimburger CM, Bouman SD, Schousboe A, Waagepetersen HS (2009) Robust glycogen shunt activity in astrocytes. Effects of glutamatergic and adrenergic agents. Neuroscience 158:284–292

    Article  CAS  PubMed  Google Scholar 

  • 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 20:6804–6810

    CAS  PubMed  Google Scholar 

Download references

Acknowledgments

The secretarial (Ms Hanne Danø) is cordially acknowledged. This work was supported by grants from The Danish Medical Research Council (22-03-250; 22-04-0314) and the Lundbeck and Novo Foundations.

Author information

Authors and Affiliations

  1. Faculty of Pharmaceutical Sciences, Department of Pharmacology and Pharmacotherapy, University of Copenhagen, Universitetsparken 2, 2100, Copenhagen, Denmark

    Arne Schousboe, Helle M. Sickmann, Anne B. Walls, Lasse K. Bak & Helle S. Waagepetersen

Authors
  1. Arne Schousboe
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Helle M. Sickmann
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Anne B. Walls
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Lasse K. Bak
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Helle S. Waagepetersen
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Arne Schousboe.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Schousboe, A., Sickmann, H.M., Walls, A.B. et al. Functional Importance of the Astrocytic Glycogen-Shunt and Glycolysis for Maintenance of an Intact Intra/Extracellular Glutamate Gradient. Neurotox Res 18, 94–99 (2010). https://doi.org/10.1007/s12640-010-9171-5

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12640-010-9171-5

Keywords

Search

Navigation