title: Regulation of oligodendrocyte development and myelination by glucose and lactate.
abstract: In the gray matter of the brain, astrocytes have been suggested to export lactate (derived from glucose or glycogen) to neurons to power their mitochondria. In the white matter, lactate can support axon function in conditions of energy deprivation, but it is not known whether lactate acts by preserving energy levels in axons or in oligodendrocytes, the myelinating processes of which are damaged rapidly in low energy conditions. Studies of cultured cells suggest that oligodendrocytes are the cell type in the brain that consumes lactate at the highest rate, in part to produce membrane lipids presumably for myelin. Here, we use pH imaging to show that oligodendrocytes in the white matter of the rat cerebellum and corpus callosum take up lactate via monocarboxylate transporters (MCTs), which we identify as MCT1 by confocal immunofluorescence and electron microscopy. Using cultured slices of developing cerebral cortex from mice in which oligodendrocyte lineage cells express GFP (green fluorescent protein) under the control of the Sox10 promoter, we show that a low glucose concentration reduces the number of oligodendrocyte lineage cells and myelination. Myelination is rescued when exogenous l-lactate is supplied. Thus, lactate can support oligodendrocyte development and myelination. In CNS diseases involving energy deprivation at times of myelination or remyelination, such as periventricular leukomalacia leading to cerebral palsy, stroke, and secondary ischemia after spinal cord injury, lactate transporters in oligodendrocytes may play an important role in minimizing the inhibition of myelination that occurs.
authors.affiliation: Department of Neuroscience, Physiology, and Pharmacology, University College London, London WC1E 6BT, UK.
authors.forename: Johanne E
authors.initials: JE
authors.lastname: Rinholm
authors.forename: Nicola B
authors.initials: NB
authors.lastname: Hamilton
authors.forename: Nicoletta
authors.initials: N
authors.lastname: Kessaris
authors.forename: William D
authors.initials: WD
authors.lastname: Richardson
authors.forename: Linda H
authors.initials: LH
authors.lastname: Bergersen
authors.forename: David
authors.initials: D
authors.lastname: Attwell
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism*; D002540:Cerebral Cortex / Q000166:cytology / Q000254:growth & development / Q000378:metabolism; D005947:Glucose / Q000378:metabolism*; D006863:Hydrogen-Ion Concentration; D019344:Lactic Acid / Q000378:metabolism*; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D027501:Monocarboxylic Acid Transporters / Q000378:metabolism; D009186:Myelin Sheath / Q000378:metabolism*; D009836:Oligodendroglia / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D051381:Rats; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D027981:Symporters / Q000378:metabolism; D046509:Tissue Culture Techniques; D000099233:Monocarboxylate Transport Protein 1
chemical_list: D005947:Glucose; D019344:Lactic Acid; D027501:Monocarboxylic Acid Transporters; D027981:Symporters; D000099233:Monocarboxylate Transport Protein 1