title: The quality of cortical network function recovery depends on localization and degree of axonal demyelination.
abstract: Myelin loss is a severe pathological hallmark common to a number of neurodegenerative diseases, including multiple sclerosis (MS). Demyelination in the central nervous system appears in the form of lesions affecting both white and gray matter structures. The functional consequences of demyelination on neuronal network and brain function are not well understood. Current therapeutic strategies for ameliorating the course of such diseases usually focus on promoting remyelination, but the effectiveness of these approaches strongly depends on the timing in relation to the disease state. In this study, we sought to characterize the time course of sensory and behavioral alterations induced by de- and remyelination to establish a rational for the use of remyelination strategies. By taking advantage of animal models of general and focal demyelination, we tested the consequences of myelin loss on the functionality of the auditory thalamocortical system: a well-studied neuronal network consisting of both white and gray matter regions. We found that general demyelination was associated with a permanent loss of the tonotopic cortical organization in vivo, and the inability to induce tone-frequency-dependent conditioned behaviors, a status persisting after remyelination. Targeted, focal lysolecithin-induced lesions in the white matter fiber tract, but not in the gray matter regions of cortex, were fully reversible at the morphological, functional and behavioral level. These findings indicate that remyelination of white and gray matter lesions have a different functional regeneration potential, with the white matter being able to regain full functionality while cortical gray matter lesions suffer from permanently altered network function. Therefore therapeutic interventions aiming for remyelination have to consider both region- and time-dependent strategies.
authors: Department of Neurology, University of Münster, Münster, Germany. Electronic address: manuela.cerina@ukmuenster.de.
authors: Manuela
authors: M
authors: Cerina
authors: Department of Neurology, University of Münster, Münster, Germany.
authors: Venu
authors: V
authors: Narayanan
authors: Department of Neurology, University of Münster, Münster, Germany.
authors: Kerstin
authors: K
authors: Göbel
authors: Department of Neurology, University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany.
authors: Stefan
authors: S
authors: Bittner
authors: Department of Neurology, University of Münster, Münster, Germany.
authors: Tobias
authors: T
authors: Ruck
authors: Department of Neurology, University of Münster, Münster, Germany.
authors: Patrick
authors: P
authors: Meuth
authors: Department of Neurology, University of Münster, Münster, Germany.
authors: Alexander M
authors: AM
authors: Herrmann
authors: Clinical Neuroimmunology and Neurochemistry, Department of Neurology, Hannover Medical School and Centre for Systems Neuroscience, Hannover, Germany.
authors: Martin
authors: M
authors: Stangel
authors: Department of Neurology, Hannover Medical School, Hannover, Germany.
authors: Viktoria
authors: V
authors: Gudi
authors: Department of Neurology, Hannover Medical School, Hannover, Germany.
authors: Thomas
authors: T
authors: Skripuletz
authors: Institute of Physiology I, University of Münster, Münster, Germany.
authors: Thiemo
authors: T
authors: Daldrup
authors: Department of Neurology, University of Münster, Münster, Germany.
authors: Heinz
authors: H
authors: Wiendl
authors: Institute of Physiology I, University of Münster, Münster, Germany.
authors: Thomas
authors: T
authors: Seidenbecher
authors: Department of Neurology, University of Münster, Münster, Germany.
authors: Petra
authors: P
authors: Ehling
authors: Department of Neurology, University of Würzburg, Würzburg, Germany.
authors: Christoph
authors: C
authors: Kleinschnitz
authors: Institute of Physiology I, University of Münster, Münster, Germany.
authors: Hans-Christian
authors: HC
authors: Pape
authors: Institute of Physiology I, University of Münster, Münster, Germany.
authors: Thomas
authors: T
authors: Budde
authors: Department of Neurology, University of Münster, Münster, Germany. Electronic address: sven.meuth@ukmuenster.de.
authors: Sven G
authors: SG
authors: Meuth
mesh_terms: D056704:Adaptive Immunity; D000818:Animals; D001522:Behavior, Animal; D002540:Cerebral Cortex / Q000503:physiopathology*; D003471:Cuprizone; D003711:Demyelinating Diseases / Q000139:chemically induced / Q000503:physiopathology* / Q000523:psychology; D004567:Electrodes, Implanted; D066128:Gray Matter / Q000473:pathology; D008244:Lysophosphatidylcholines; D051379:Mice; D008810:Mice, Inbred C57BL; D009186:Myelin Sheath / Q000473:pathology; D009415:Nerve Net / Q000503:physiopathology*; D020127:Recovery of Function; D012677:Sensation; D066127:White Matter / Q000473:pathology
chemical_list: D008244:Lysophosphatidylcholines; D003471:Cuprizone
keywords: Demyelination; Gray matter lesion; Remyelination; Thalamocortical system; White matter lesion