QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

HOME  |   SEARCH  |   ARCHIVE  |   SUBSCRIBE  |   CONTACT  |   HELP

This Article Full Text Full Text (PDF) Submit an eLetter Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (87) Citing Articles via Google Scholar Google Scholar Articles by Wender, R. Articles by Ransom, B. R. Search for Related Content PubMed PubMed Citation Articles by Wender, R. Articles by Ransom, B. R.

 Previous Article  |  Next Article 

The Journal of Neuroscience, September 15, 2000, 20(18):6804-6810

Astrocytic Glycogen Influences Axon Function and Survival during Glucose Deprivation in Central White Matter

Regina Wender^{1, 2}, Angus M. Brown¹, Robert Fern¹, Raymond A. Swanson³, Kevin Farrell³, and Bruce R. Ransom^{1, 2}

Departments of ¹ Neurology and ² Physiology and Biophysics, University of Washington School of Medicine, Seattle, Washington 98195, and ³ Department of Neurology, University of California, San Francisco, and Veterans Affairs Medical Center, San Francisco, California 94121

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 ~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, -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.

Key words: astrocytes; -cyano-4-hydroxycinnamate; glucose; hypoglycemia; lactate; p-chloromercuribenzene sulfonic acid; quercetin; rat optic nerve

---

Copyright © 2000 Society for Neuroscience  0270-6474/00/20186804-07$05.00/0

This article has been cited by other articles:

				D. Lovatt, U. Sonnewald, H. S. Waagepetersen, A. Schousboe, W. He, J. H.-C. Lin, X. Han, T. Takano, S. Wang, F. J. Sim, et al. The Transcriptome and Metabolic Gene Signature of Protoplasmic Astrocytes in the Adult Murine Cortex J. Neurosci., November 7, 2007; 27(45): 12255 - 12266. [Abstract] [Full Text] [PDF]

				B. S. McEwen Physiology and Neurobiology of Stress and Adaptation: Central Role of the Brain Physiol Rev, July 1, 2007; 87(3): 873 - 904. [Abstract] [Full Text] [PDF]

				Y.-C. Tseng, C.-J. Huang, J. C.-H. Chang, W.-Y. Teng, O. Baba, M.-J. Fann, and P.-P. Hwang Glycogen phosphorylase in glycogen-rich cells is involved in the energy supply for ion regulation in fish gill epithelia Am J Physiol Regulatory Integrative Comp Physiol, July 1, 2007; 293(1): R482 - R491. [Abstract] [Full Text] [PDF]

				S. W. Suh, J. P. Bergher, C. M. Anderson, J. L. Treadway, K. Fosgerau, and R. A. Swanson 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)propyl]-1H-indole-2-carboxamide) J. Pharmacol. Exp. Ther., April 1, 2007; 321(1): 45 - 50. [Abstract] [Full Text] [PDF]

				G. Oz, E. R. Seaquist, A. Kumar, A. B. Criego, L. E. Benedict, J. P. Rao, P.-G. Henry, P.-F. Van De Moortele, and R. Gruetter Human brain glycogen content and metabolism: implications on its role in brain energy metabolism Am J Physiol Endocrinol Metab, March 1, 2007; 292(3): E946 - E951. [Abstract] [Full Text] [PDF]

				A. Joardar, A. K. Sen, and S. Das Docosahexaenoic acid facilitates cell maturation and {beta}-adrenergic transmission in astrocytes J. Lipid Res., March 1, 2006; 47(3): 571 - 581. [Abstract] [Full Text] [PDF]

				L. Allen, S. Anderson, R. Wender, P. Meakin, B. R. Ransom, D. E. Ray, and A. M. Brown Fructose Supports Energy Metabolism of Some, But Not All, Axons in Adult Mouse Optic Nerve J Neurophysiol, March 1, 2006; 95(3): 1917 - 1925. [Abstract] [Full Text] [PDF]

				S. W. Suh, K. Aoyama, Y. Matsumori, J. Liu, and R. A. Swanson Pyruvate Administered After Severe Hypoglycemia Reduces Neuronal Death and Cognitive Impairment Diabetes, May 1, 2005; 54(5): 1452 - 1458. [Abstract] [Full Text] [PDF]

				B. V. Bui, M. Kalloniatis, and A. J. Vingrys Retinal Function Loss after Monocarboxylate Transport Inhibition Invest. Ophthalmol. Vis. Sci., February 1, 2004; 45(2): 584 - 593. [Abstract] [Full Text] [PDF]

				M. C. Kruit, M. A. van Buchem, P. A. M. Hofman, J. T. N. Bakkers, G. M. Terwindt, M. D. Ferrari, and L. J. Launer Migraine as a Risk Factor for Subclinical Brain Lesions JAMA, January 28, 2004; 291(4): 427 - 434. [Abstract] [Full Text] [PDF]

				M. CHESLER Regulation and Modulation of pH in the Brain Physiol Rev, October 1, 2003; 83(4): 1183 - 1221. [Abstract] [Full Text] [PDF]

				B. V. Bui, M. Kalloniatis, and A. J. Vingrys The Contribution of Glycolytic and Oxidative Pathways to Retinal Photoreceptor Function Invest. Ophthalmol. Vis. Sci., June 1, 2003; 44(6): 2708 - 2715. [Abstract] [Full Text] [PDF]

				A. M Brown, S. B. Tekkok, and B. R Ransom Glycogen regulation and functional role in mouse white matter J. Physiol., June 1, 2003; 549(2): 501 - 512. [Abstract] [Full Text] [PDF]

				M. P. Goldberg and B. R. Ransom New Light on White Matter Stroke, February 1, 2003; 34(2): 330 - 332. [Full Text] [PDF]

				C. Vega, J.-L. Martiel, D. Drouhault, M.-F. Burckhart, and J. A Coles Uptake of locally applied deoxyglucose, glucose and lactate by axons and Schwann cells of rat vagus nerve J. Physiol., January 15, 2003; 546(2): 551 - 564. [Abstract] [Full Text] [PDF]

				A. M. Brown and B. R. Ransom Neuroprotective Effects of Increased Extracellular Ca2+ During Aglycemia in White Matter J Neurophysiol, September 1, 2002; 88(3): 1302 - 1307. [Abstract] [Full Text] [PDF]

				J. Kong, P. N. Shepel, C. P. Holden, M. Mackiewicz, A. I. Pack, and J. D. Geiger Brain Glycogen Decreases with Increased Periods of Wakefulness: Implications for Homeostatic Drive to Sleep J. Neurosci., July 1, 2002; 22(13): 5581 - 5587. [Abstract] [Full Text] [PDF]

Home  |   Search  |   Archive  |   Subscribe  |   Contact  |   Help