Astrocytic glycogen influences axon function and survival during glucose deprivation in central white matter
Open accessAbstract
We tested the hypothesis that astrocytic glycogen sustains axon function during and enhances axon survival after 60 min of glucose deprivation. Axon function in the rat optic nerve (RON), a CNS white matter tract, was monitored by measuring the area of the stimulus-evoked compound action potential (CAP). Switching to glucose-free artificial CSF (aCSF) had no effect on the CAP area for approximately 30 min, after which the CAP rapidly failed. Exposure to glucose-free aCSF for 60 min caused irreversible injury, which was measured as incomplete recovery of the CAP. Glycogen content of the RON fell to a low stable level 30 min after glucose withdrawal, compatible with rapid use in the absence of glucose. An increase of glycogen content induced by high-glucose pretreatment increased the latency to CAP failure and improved CAP recovery. Conversely, a decrease of glycogen content induced by norepinephrine pretreatment decreased the latency to CAP failure and reduced CAP recovery. To determine whether lactate represented the fuel derived from glycogen and shuttled to axons, we used the lactate transport blockers quercetin, alpha-cyano-4-hydroxycinnamic acid (4-CIN), and p-chloromercuribenzene sulfonic acid (pCMBS). All transport blockers, when applied during glucose withdrawal, decreased latency to CAP failure and decreased CAP recovery. The inhibitors 4-CIN and pCMBS, but not quercetin, blocked lactate uptake by axons. These results indicated that, in the absence of glucose, astrocytic glycogen was broken down to lactate, which was transferred to axons for fuel.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Glycogen in astrocytes is able to sustain axon function during glucose deprivation in central nervous system white matter.
“although it is noteworthy that glycogen in astrocytes is able to sustain axon function during glucose deprivation in central nervous system white matter.65”
From Sleep Deprivation and Circadian Disruption (2015) · cites this paper as [65]
Glycogen in astrocytes is able to sustain axon function during glucose deprivation in CNS white matter.
“It is noteworthy that glycogen in astrocytes is able to sustain axon function during glucose deprivation in central nervous system (CNS) white matter.28”
From Protective and damaging effects of stress mediators: central role of the brain (2006) · cites this paper as [28]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
PROTEIN MEASUREMENT WITH THE FOLIN PHENOL REAGENT
Lowry, O. H., Rosebrough, N., Farr, A. L., & Randall, R. (1951) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)52451-6 · Cited by 315,771 · see citing works
Sokoloff, L., Reivich, M., Kennedy, C., Rosiers, M. H. D., Patlak, C. S., Pettigrew, K. D., Sakurada, O., & Shinohara, M. (1977) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.1977.tb10649.x · Cited by 6,000 · see citing works
Siesjö, B. K. (1978) · Medical Entomology and Zoology · Cited by 1,426 · see citing works
The proton-linked monocarboxylate transporter (MCT) family: structure, function and regulation
Halestrap, A. P., & Price, N. T. (1999) · Biochemical Journal · doi:10.1042/bj3430281 · Cited by 1,350 · see citing works
(1976) · Medical Entomology and Zoology · Cited by 1,328 · see citing works
Transport of lactate and other monocarboxylates across mammalian plasma membranes
Poole, R. C., & Halestrap, A. P. (1993) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.1993.264.4.c761 · Cited by 747 · see citing works
A comparison of three methods of glycogen measurement in tissues
Passonneau, J. V., & Lauderdale, V. R. (1974) · Analytical Biochemistry · doi:10.1016/0003-2697(74)90248-6 · Cited by 744 · see citing works
Circulation and Energy Metabolism of the Brain
Clarke, D. D., & Sokoloff, L. (1999) · Cited by 732 · see citing works
Goldberg, M. P., & Choi, D. W. (1993) · Journal of Neuroscience · doi:10.1523/jneurosci.13-08-03510.1993 · Cited by 693 · see citing works
Welsh, F. A., & Shapiro, H. M. (1979) · Anesthesiology · doi:10.1097/00000542-197904000-00027 · Cited by 647 · see citing works
Lactate-supported synaptic function in the rat hippocampal slice preparation.
Schurr, A., West, C. A., & Rigor, B. (1988) · Science · doi:10.1126/science.3375817 · Cited by 594 · see citing works
Glycogen in astrocytes: possible function as lactate supply for neighboring cells
Dringen, R., Gebhardt, R., & Hamprecht, B. (1993) · Brain Research · doi:10.1016/0006-8993(93)91429-v · Cited by 536 · see citing works
Ia, S., & Erecińska, M. (1994) · Journal of Neuroscience · doi:10.1523/jneurosci.14-08-05068.1994 · Cited by 477 · see citing works
Lactate transport in skeletal muscle — role and regulation of the monocarboxylate transporter
Juel, C., & Halestrap, A. P. (1999) · The Journal of Physiology · doi:10.1111/j.1469-7793.1999.0633s.x · Cited by 448 · see citing works
Selective distribution of lactate dehydrogenase isoenzymes in neurons and astrocytes of human brain
Bittar, P. G., Charnay, Y., Pellerin, L., Bouras, C., & Magistretti, P. J. (1996) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1097/00004647-199611000-00001 · Cited by 423 · see citing works
Lactate released by Muller glial cells is metabolized by photoreceptors from mammalian retina
Poitry‐Yamate, C. L., Poitry, S., & Tsacopoulos, M. (1995) · Journal of Neuroscience · doi:10.1523/jneurosci.15-07-05179.1995 · Cited by 410 · see citing works
Bröer, S., Rahman, B., Pellegri, G., Pellerin, L., Martin, J., Verleysdonk, S., Hamprecht, B., & Magistretti, P. J. (1997) · Journal of Biological Chemistry · doi:10.1074/jbc.272.48.30096 · Cited by 347 · see citing works
Lactate-proton cotransport in skeletal muscle
Juel, C. (1997) · Physiological Reviews · doi:10.1152/physrev.1997.77.2.321 · Cited by 313 · see citing works
Bröer, S., SCHNEIDER, H.-P., Bröer, A., Rahman, B., Hamprecht, B., & Deitmer, J. W. (1998) · Biochemical Journal · doi:10.1042/bj3330167 · Cited by 312 · see citing works
Characterization of the high-affinity monocarboxylate transporter MCT2 in Xenopus laevis oocytes
Bröer, S., Bröer, A., SCHNEIDER, H.-P., Stegen, C. F., Halestrap, A. P., & Deitmer, J. W. (1999) · Biochemical Journal · doi:10.1042/0264-6021:3410529 · Cited by 273 · see citing works
Sensory stimulation induces local cerebral glycogenolysis: Demonstration by autoradiography
Swanson, R. A., Morton, M. M., Sagar, S. M., & Sharp, F. R. (1992) · Neuroscience · doi:10.1016/0306-4522(92)90329-z · Cited by 237 · see citing works
Self-citationGlial Glycogen Stores Affect Neuronal Survival during Glucose Deprivation in vitro
Swanson, R. A., & Choi, D. W. (1993) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1038/jcbfm.1993.19 · Cited by 231 · see citing works
Self-citationCataldo, A. M., & Broadwell, R. D. (1986) · Journal of Neurocytology · doi:10.1007/bf01611733 · Cited by 217 · see citing works
Role of extracellular calcium in anoxic injury of mammalian central white matter.
Stys, P. K., Ransom, B. R., Waxman, S. G., & Davis, P. K. (1990) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.87.11.4212 · Cited by 205 · see citing works
Self-citationCataldo, A. M., & Broadwell, R. D. (1986) · Journal of Electron Microscopy Technique · doi:10.1002/jemt.1060030406 · Cited by 196 · see citing works
Stys, P. K., Ransom, B. R., & Waxman, S. G. (1991) · Brain Research · doi:10.1016/0006-8993(91)91154-s · Cited by 195 · see citing works
Jackson, V. N., & Halestrap, A. P. (1996) · Journal of Biological Chemistry · doi:10.1074/jbc.271.2.861 · Cited by 173 · see citing works
Izumi, Y., Benz, A. M., Katsuki, H., & Zorumski, C. F. (1997) · Journal of Neuroscience · doi:10.1523/jneurosci.17-24-09448.1997 · Cited by 166 · see citing works
Quach, T., Rose, C., & Schwartz, J.-C. (1978) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.1978.tb10464.x · Cited by 139 · see citing works
Monocarboxylate transporter expression in mouse brain
Koehler-Stec, E. M., Simpson, I. A., Vannucci, S. J., Landschulz, K. T., & Landschulz, W. H. (1998) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.1998.275.3.e516 · Cited by 136 · see citing works
Dringen, R., & Hamprecht, B. (1992) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.1992.tb09750.x · Cited by 134 · see citing works
Effects of lactate and pyruvate on glucose deprivation in rat hippocampal slices
Izumi, Y., Benz, A. M., Zorumski, C. F., & Olney, J. W. (1994) · Neuroreport · doi:10.1097/00001756-199401000-00021 · Cited by 132 · see citing works
Lactate Metabolism and Its Effects on Glucose Metabolism in an Excised Neural Tissue
Larrabee, M. G. (1995) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.1995.64041734.x · Cited by 129 · see citing works
Inhibition of lactate transport and glycolysis in Ehrlich ascites tumor cells by bioflavonoids
Belt, J. A., Thomas, J. A., Buchsbaum, R., & Racker, E. (1979) · Biochemistry · doi:10.1021/bi00583a011 · Cited by 128 · see citing works
EDLUND, G. L., & Halestrap, A. P. (1988) · Biochemical Journal · doi:10.1042/bj2490117 · Cited by 102 · see citing works
THE CYTOCHEMISTRY OF NORMAL AND REACTIVE ASTROCYTES
Friede, R. L. (1962) · Journal of Neuropathology & Experimental Neurology · doi:10.1097/00005072-196207000-00015 · Cited by 100 · see citing works
Regulation of glycogenolysis by neurotransmitters in the central nervous system.
Magistretti, P. J. (1988) · PubMed · Cited by 96 · see citing works
Regional brain glycogen stores and metabolism during complete global ischaemia
Swanson, R. A., Sagar, S. M., & Sharp, F. R. (1989) · Neurological Research · doi:10.1080/01616412.1989.11739856 · Cited by 95 · see citing works
Self-citationSignificance of the potassium signal from neurones to glial cells
Pentreath, V. W., & Kai-Kai, M. A. (1982) · Nature · doi:10.1038/295059a0 · Cited by 94 · see citing works
Glycogen synthesis in the astrocyte: from glycogenin to proglycogen to glycogen
Lomako, J., Lomako, W. M., Whelan, W. J., Dombro, R. S., Neary, J. T., & Norenberg, M. D. (1993) · The FASEB Journal · doi:10.1096/fasebj.7.14.8224611 · Cited by 94 · see citing works
Magistretti, P. J., Sorg, O., & Martin, J. (1993) · Elsevier eBooks · doi:10.1016/b978-0-12-511370-0.50015-1 · Cited by 84 · see citing works
Axon Conduction and Survival in CNS White Matter During Energy Deprivation: A Developmental Study
Fern, R. F., Davis, P. K., Waxman, S. G., & Ransom, B. R. (1998) · Journal of Neurophysiology · doi:10.1152/jn.1998.79.1.95 · Cited by 83 · see citing works
Self-citationGlial metabolism: alteration by potassium levels comparable to those during neural activity
Orkand, P. M., Bracho, H., & Orkand, R. K. (1973) · Brain Research · doi:10.1016/0006-8993(73)90315-6 · Cited by 73 · see citing works
Swanson, R. A., Yu, A. C. H., Sharp, F. R., & Chan, P. H. (1989) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.1989.tb09180.x · Cited by 71 · see citing works
Self-citationMcKenna, M. C., Tildón, J. T., Stevenson, J., Hopkins, I. B., Huang, X., & Couto, R. (1998) · Developmental Neuroscience · doi:10.1159/000017325 · Cited by 67 · see citing works
Inhibition of lactate export by quercetin acidifies rat glial cells in vitro
Volk, C., Kempski, B., & Kempski, O. S. (1997) · Neuroscience Letters · doi:10.1016/s0304-3940(97)13420-6 · Cited by 52 · see citing works
Simulation of aspects of ischemia in cell culture: Changes in lactate compartmentation
Walz, W., & Mukerji, S. (1990) · Glia · doi:10.1002/glia.440030611 · Cited by 47 · see citing works
Effect of Insulin on the Synthesis of Glycogen in Cerebral Cortical Slices of Alloxan Diabetic Rats
Prasannan, K. G., & Subrahmanyam, K. (1968) · Endocrinology · doi:10.1210/endo-82-1-1 · Cited by 40 · see citing works
Larrabee, M. G. (1983) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.1983.tb13562.x · Cited by 40 · see citing works
Glycogen Metabolism in Quail Embryo Muscle
Lomako, J., Lomako, W. M., & Whelan, W. J. (1995) · European Journal of Biochemistry · doi:10.1111/j.1432-1033.1995.343_c.x · Cited by 31 · see citing works
Glucose transporter proteins in brain: Delivery of glucose to neurons and glia
Vannucci, S. J., Maher, F., & Simpson, I. A. (1997) · Glia · doi:10.1002/(sici)1098-1136(199709)21:1
Flagged first, then by citations
Cited by
Sorted by citations
Physiology and neurobiology of stress and adaptation: central role of the brain
McEwen, B. S. (2007) · Physiological Reviews · doi:10.1152/physrev.00041.2006 · Cited by 4,981 · see citing works
Brain insulin resistance in type 2 diabetes and Alzheimer disease: concepts and conundrums
Arnold, S. E., Arvanitakis, Z., Macauley-Rambach, S. L., Koenig, A. M., Wang, H.-Y., Ahima, R. S., Craft, S., Gandy, S., Buettner, C., Stoeckel, L. E., et al. (2018) · Nature Reviews Neurology · doi:10.1038/nrneurol.2017.185 · Cited by 1,597 · see citing works
Protective and damaging effects of stress mediators: central role of the brain
McEwen, B. S. (2006) · Dialogues in Clinical Neuroscience · doi:10.31887/dcns.2006.8.4/bmcewen · Cited by 1,220 · see citing works
Myelination and the trophic support of long axons
Nave, K.-A. (2010) · Nature Reviews Neuroscience · doi:10.1038/nrn2797 · Cited by 648 · see citing works
Sleep deprivation as a neurobiologic and physiologic stressor: allostasis and allostatic load
McEwen, B. S. (2006) · Metabolism · doi:10.1016/j.metabol.2006.07.008 · Cited by 624 · see citing works
Glial cells in (patho)physiology
Parpura, V., Heneka, M. T., Montana, V., Oliet, S. H. R., Schousboe, A., Haydon, P. G., Stout, R. F., Spray, D. C., Reichenbach, A., Pannicke, T., et al. (2012) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2012.07664.x · Cited by 561 · see citing works
Sleep Deprivation and Circadian Disruption
McEwen, B. S., & Karatsoreos, I. N. (2015) · Sleep Medicine Clinics · doi:10.1016/j.jsmc.2014.11.007 · Cited by 338 · see citing works
Brown, A. M. (2004) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2004.02421.x · Cited by 308 · see citing works
Self-citationKong, J., Shepel, P. N., Holden, C. P., Mackiewicz, M., Pack, A. I., & Geiger, J. D. (2002) · The Journal of Neuroscience · doi:10.1523/jneurosci.22-13-05581.2002 · Cited by 281 · see citing works
Fernandez, C. G., Hamby, M. E., McReynolds, M. L., & Ray, W. J. (2019) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2019.00014 · Cited by 277 · see citing works
Glycogen regulation and functional role in mouse white matter
Brown, A. M., Tekkök, S. B., & Ransom, B. R. (2003) · The Journal of Physiology · doi:10.1113/jphysiol.2003.042416 · Cited by 243 · see citing works
Self-citationTekkök, S. B., Brown, A. M., Westenbroek, R., Pellerin, L., & Ransom, B. R. (2005) · Journal of Neuroscience Research · doi:10.1002/jnr.20573 · Cited by 224 · see citing works
Self-citationAstrocytic contributions to bioenergetics of cerebral ischemia
Dienel, G. A., & Hertz, L. (2005) · Glia · doi:10.1002/glia.20157 · Cited by 150 · see citing works
Oligodendroglial fatty acid metabolism as a central nervous system energy reserve
Asadollahi, E., Trevisiol, A., Saab, A. S., Looser, Z. J., Dibaj, P., Ebrahimi, R., Kusch, K., Ruhwedel, T., Möbius, W., Jahn, O., et al. (2024) · Nature Neuroscience · doi:10.1038/s41593-024-01749-6 · Cited by 130 · see citing works
The astrocyte-neuron lactate shuttle: a challenge of a challenge
Hertz, L. (2004) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1097/00004647-200411000-00008 · Cited by 124 · see citing works
Wang, X.-J., Zhang, S., Yan, Z.-Q., Zhao, Y.-X., Zhou, H.-Y., Wang, Y., Lu, G.-Q., & Zhang, J.-D. (2011) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2011.01.032 · Cited by 108 · see citing works
Puente, E. C., Silverstein, J., Bree, A. J., Musikantow, D. R., Wozniak, D. F., Maloney, S., Daphna-Iken, D., & Fisher, S. J. (2010) · Diabetes · doi:10.2337/db09-1495 · Cited by 103 · see citing works
Metabolic Vulnerability in the Neurodegenerative Disease Glaucoma
Inman, D. M., & Harun-Or-Rashid, M. (2017) · Frontiers in Neuroscience · doi:10.3389/fnins.2017.00146 · Cited by 88 · see citing works
Regulation of neuron-astrocyte metabolic coupling across the sleep-wake cycle
Petit, J.-M., & Magistretti, P. J. (2016) · Neuroscience · doi:10.1016/j.neuroscience.2015.12.007 · Cited by 92 · see citing works
Metabolic substrates other than glucose support axon function in central white matter
Brown, A. M., Wender, R., & Ransom, B. R. (2001) · Journal of Neuroscience Research · doi:10.1002/jnr.10081 · Cited by 85 · see citing works
Self-citationWhy does the brain (not) have glycogen?
DiNuzzo, M., Maraviglia, B., & Giove, F. (2011) · BioEssays · doi:10.1002/bies.201000151 · Cited by 53 · see citing works
Stys, P. K. (2011) · Trends in Neurosciences · doi:10.1016/j.tins.2011.06.004 · Cited by 51 · see citing works
A role for CO<sub>2</sub> and bicarbonate transporters in metabolic exchanges in the brain
Deitmer, J. W. (2002) · Journal of Neurochemistry · doi:10.1046/j.0022-3042.2002.00765.x · Cited by 36 · see citing works
- Authors
- Wender, R., Brown, A. M., Fern, R., Swanson, R. A., Farrell, K., & Ransom, B. R.
- Affiliations
- University of Washington (US)
- Pediatrics and Genetics (US)
- San Francisco VA Medical Center (US)
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2000-09-15
- Volume
- 20
- Issue
- 18
- Pages
- 6804-6810
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC6772835
- OpenAlex
- W1928529925
- Cited by
- 374
- References
- 51
- Citations by year
- 2026: 2 · 2025: 8 · 2024: 11 · 2023: 13 · 2022: 8 · 2021: 10 · 2020: 21 · 2019: 18 · 2018: 22 · 2017: 19 · 2016: 14 · 2015: 12 · 2014: 23 · 2013: 15 · 2012: 21
- FWCI
- 5.29
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Neuroscience (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Yale University
- National Institutes of Health (5r01ns031914-07)
- National Institute of Neurological Disorders and Stroke (T32NS007144, R01NS015589, NS31914, NS15589, T32NS07144)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Neurology › Neurological Disorders and Treatments
- Life Sciences › Neuroscience › Neurology › Neurological Disease Mechanisms and Treatments
- Keywords
- glucose deprivation, axon survival, optic nerve, compound action potential, lactate transport, lactate shuttle, norepinephrine, quercetin, axonal energy metabolism
- MeSH terms
- Action Potentials, Animals, Astrocytes, Axons, Biological Transport, Cell Survival, 4-Chloromercuribenzenesulfonate, Coumaric Acids, Culture Media, Enzyme Inhibitors, Glucose, Glycogen, Optic Nerve, Quercetin, Reaction Time, Lactic Acid, Rats, Long-Evans, Rats, In Vitro Techniques
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
