Metabolic substrates other than glucose support axon function in central white matter

We tested the hypothesis that non‐glucose energy sources can support axon function in the rat optic nerve. Axon function was assessed by monitoring the stimulus‐evoked compound action potential (CAP). CAP was maintained at full amplitude for 2 hr in 10 mM glucose. 20 mM lactate, 20 mM pyruvate, 10 mM fructose, or 10 mM mannose supported axon function as effectively as did glucose, and 10 mM glutamine provided partial support, but β‐hydroxybutyrate, octanoate, sorbitol, alanine, aspartate, and glutamate failed to support axon function. Our results indicated that a variety of compounds can sustain function in CNS myelinated axons. Axons probably use lactate, pyruvate, and glutamine directly as energy substrates, whereas mannose and fructose could be shuttled through astrocytes to lactate, which is then exported to axons. © 2001 Wiley‐Liss, Inc.

[1]  M. Raizada,et al.  Identification of a System N‐Like Na+‐Dependent Glutamine Transport Activity in Rat Brain Neurons , 1997, Journal of neurochemistry.

[2]  M. Tsacopoulos,et al.  Glial cells transform glucose to alanine, which fuels the neurons in the honeybee retina , 1994, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[3]  G. Mealing,et al.  Novel Injury Mechanism in Anoxia and Trauma of Spinal Cord White Matter: Glutamate Release via Reverse Na+-dependent Glutamate Transport , 1999, The Journal of Neuroscience.

[4]  P. Grafe,et al.  Lactate-proton co-transport and its contribution to interstitial acidification during hypoxia in isolated rat spinal roots , 1993, Neuroscience.

[5]  H. Sloviter,et al.  The isolated, perfused rat brain preparation metabolizes manmose but not maltose 1 , 1970 .

[6]  R. Dringen,et al.  Differences in glycogen metabolism in astroglia‐rich primary cultures and sorbitol‐selected astroglial cultures derived from mouse brain , 1993, Glia.

[7]  P. Magistretti,et al.  Cell-specific localization of monocarboxylate transporters, MCT1 and MCT2, in the adult mouse brain revealed by double immunohistochemical labeling and confocal microscopy , 2000, Neuroscience.

[8]  H. Sloviter,et al.  The isolated, persed rat brain preparation metabolizes mannose but not maltose. , 1970, Journal of neurochemistry.

[9]  S. Kety,et al.  The circulation and energy metabolism of the brain. , 1963, Clinical neurosurgery.

[10]  J. de Vellis,et al.  Capacity for substrate utilization in oxidative metabolism by neurons, astrocytes, and oligodendrocytes from developing brain in primary culture , 1987, Journal of neuroscience research.

[11]  Peter K. Stys,et al.  Compound action potential of nerve recorded by suction electrode: a theoretical and experimental analysis , 1991, Brain Research.

[12]  B. Ransom,et al.  Does astrocytic glycogen benefit axon function and survival in CNS white matter during glucose deprivation? , 1997, Glia.

[13]  A. Halestrap,et al.  The Kinetics, Substrate, and Inhibitor Specificity of the Monocarboxylate (Lactate) Transporter of Rat Liver Cells Determined Using the Fluorescent Intracellular pH Indicator, 2′,7′-Bis(carboxyethyl)-5(6)-carboxyfluorescein (*) , 1996, The Journal of Biological Chemistry.

[14]  R. Swanson,et al.  Astrocyte glutamate transport: Review of properties, regulation, and physiological functions , 2000, Glia.

[15]  J. Puymirat,et al.  Effect of Polyunsaturated Fatty Acids on Fetal Mouse Brain Cells in Culture in a Chemically Defined Medium , 1983, Journal of neurochemistry.

[16]  A. Nehlig Respective roles of glucose and ketone bodies as substrates for cerebral energy metabolism in the suckling rat. , 1996, Developmental neuroscience.

[17]  C. Sansom,et al.  Studies of the membrane topology of the rat erythrocyte H+/lactate cotransporter (MCT1). , 1996, The Biochemical journal.

[18]  A. Schousboe,et al.  Trafficking between glia and neurons of TCA cycle intermediates and related metabolites , 1997, Glia.

[19]  Jean X. Jiang,et al.  Characterization of an N-system Amino Acid Transporter Expressed in Retina and Its Involvement in Glutamine Transport* , 2001, The Journal of Biological Chemistry.

[20]  F. Sharp,et al.  Glutamate Increases Glycogen Content and Reduces Glucose Utilization in Primary Astrocyte Culture , 1990, Journal of neurochemistry.

[21]  P. Magistretti,et al.  Selective Distribution of Lactate Dehydrogenase Isoenzymes in Neurons and Astrocytes of Human Brain , 1996, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[22]  N. Auestad,et al.  Fatty Acid Oxidation and Ketogenesis by Astrocytes in Primary Culture , 1991, Journal of neurochemistry.

[23]  N. Brookes Intracellular pH as a regulatory signal in astrocyte metabolism , 1997, Glia.

[24]  Y. Izumi,et al.  Monocarboxylates (pyruvate and lactate) as alternative energy substrates for the induction of long-term potentiation in rat hippocampal slices , 1997, Neuroscience Letters.

[25]  S. Waxman,et al.  Anoxic injury of central myelinated axons: ionic mechanisms and pharmacology. , 1993, Research publications - Association for Research in Nervous and Mental Disease.

[26]  M. Tsacopoulos,et al.  Lactate released by Muller glial cells is metabolized by photoreceptors from mammalian retina , 1995, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[27]  R. Dringen,et al.  Metabolic pathways for glucose in astrocytes , 1997, Glia.

[28]  A. Schurr,et al.  Lactate-supported synaptic function in the rat hippocampal slice preparation. , 1988, Science.

[29]  R A Swanson,et al.  Astrocytic Glycogen Influences Axon Function and Survival during Glucose Deprivation in Central White Matter , 2000, The Journal of Neuroscience.