title: ERK1/2 Activation in Preexisting Oligodendrocytes of Adult Mice Drives New Myelin Synthesis and Enhanced CNS Function.
abstract: Growing evidence shows that mechanisms controlling CNS plasticity extend beyond the synapse and that alterations in myelin can modify conduction velocity, leading to changes in neural circuitry. Although it is widely accepted that newly generated oligodendrocytes (OLs) produce myelin in the adult CNS, the contribution of preexisting OLs to functional myelin remodeling is not known. Here, we show that sustained activation of extracellular signal-regulated kinases 1 and 2 (ERK1/2) in preexisting OLs of adult mice is sufficient to drive increased myelin thickness, faster conduction speeds, and enhanced hippocampal-dependent emotional learning. Although preexisting OLs do not normally contribute to remyelination, we show that sustained activation of ERK1/2 renders them able to do so. These data suggest that strategies designed to push mature OLs to reinitiate myelination may be beneficial both for enhancing remyelination in demyelinating diseases and for increasing neural plasticity in the adult CNS.
  
  
  
  Myelin is a crucial regulator of CNS plasticity, function, and repair. Although it is generally accepted that new myelin production in the adult CNS is initiated by newly generated oligodendrocytes (OLs), great interest remains in additionally driving mature preexisting OLs to make myelin. The ability to induce myelination by the larger population of preexisting OLs carries the potential for enhanced remyelination in demyelinating diseases and increased neural plasticity in the adult CNS. Here, we show that sustained activation of the extracellular signal-regulated kinases 1 and 2 (ERK1/2) signaling pathway is sufficient to drive mature OLs in the adult mouse CNS to reinitiate myelination, leading to new myelin wraps and functional changes.
authors: Center for Neuroscience.
authors: Marisa A
authors: 0000-0002-2486-0457
authors: MA
authors: Jeffries
authors: Department of Pediatrics, Division of Neurology, and.
authors: Kelly
authors: K
authors: Urbanek
authors: Department of Otolaryngology, University of Pittsburgh, Pittsburgh, Pennsylvania 15224, and.
authors: Lester
authors: L
authors: Torres
authors: Department of Pharmacology and Chemical Biology, University of Pittsburgh, Pittsburgh, Pennsylvania 15261.
authors: Stacy Gelhaus
authors: 0000-0001-9083-6933
authors: SG
authors: Wendell
authors: Center for Neuroscience, Department of Otolaryngology, University of Pittsburgh, Pittsburgh, Pennsylvania 15224, and.
authors: Maria E
authors: ME
authors: Rubio
authors: Center for Neuroscience, Department of Pediatrics, Division of Neurology, and sharyl.fyffemaricich@chp.edu.
authors: Sharyl L
authors: 0000-0001-5843-2023
authors: SL
authors: Fyffe-Maricich
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D002490:Central Nervous System / Q000502:physiology*; D003213:Conditioning, Psychological / Q000502:physiology; D003711:Demyelinating Diseases / Q000139:chemically induced / Q000473:pathology* / Q000503:physiopathology; D004195:Disease Models, Animal; D016057:Evoked Potentials, Auditory, Brain Stem / Q000235:genetics; D005106:Exploratory Behavior / Q000502:physiology; D005239:Fear / Q000502:physiology; D005699:Galactosylceramides / Q000378:metabolism; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D008245:Lysophospholipase / Q000633:toxicity; D048369:MAP Kinase Kinase 1 / Q000235:genetics / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D046529:Microscopy, Electron, Transmission; D048052:Mitogen-Activated Protein Kinase 3 / Q000235:genetics / Q000378:metabolism*; D053580:Muscle Strength / Q000235:genetics; D018991:Myelin Proteolipid Protein / Q000235:genetics / Q000378:metabolism; D009186:Myelin Sheath / Q000378:metabolism* / Q000648:ultrastructure; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009836:Oligodendroglia / Q000502:physiology* / Q000648:ultrastructure; D011597:Psychomotor Performance / Q000502:physiology; D012333:RNA, Messenger / Q000378:metabolism; D021641:Recognition, Psychology / Q000502:physiology; D053719:Tandem Mass Spectrometry
chemical_list: D005699:Galactosylceramides; D018991:Myelin Proteolipid Protein; D009419:Nerve Tissue Proteins; C047516:Plp1 protein, mouse; D012333:RNA, Messenger; C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins; D048052:Mitogen-Activated Protein Kinase 3; D048369:MAP Kinase Kinase 1; C482127:Map2k1 protein, mouse; D008245:Lysophospholipase
keywords: ERK MAP kinase; intracellular signaling; myelin; myelin plasticity; oligodendrocyte; remyelination