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Panglial gap junctional communication is essential for maintenance of myelin in the CNS

Item Type:Article
Title:Panglial gap junctional communication is essential for maintenance of myelin in the CNS
Creators Name:Tress, O. and Maglione, M. and May, D. and Pivneva, T. and Richter, N. and Seyfarth, J. and Binder, S. and Zlomuzica, A. and Seifert, G. and Theis, M. and Dere, E. and Kettenmann, H. and Willecke, K.
Abstract:In this study, we have investigated the contribution of oligodendrocytic connexin47 (Cx47) and astrocytic Cx30 to panglial gap junctional networks as well as myelin maintenance and function by deletion of both connexin coding DNAs in mice. Biocytin injections revealed complete disruption of oligodendrocyte-to-astrocyte coupling in the white matter of 10- to 15-d-old Cx30/Cx47 double-deficient mice, while oligodendrocyte-to-oligodendrocyte coupling was maintained. There were no quantitative differences regarding cellular networks in acute brain slices obtained from Cx30/Cx47 double-null mice and control littermates, probably caused by the upregulation of oligodendrocytic Cx32 in Cx30/Cx47 double-deficient mice. We observed early onset myelin pathology, and ∼40% of Cx30/Cx47 double-deficient animals died within 42 to 90 d after birth, accompanied by severe motor impairments. Histological and ultrastructural analyses revealed severe vacuolization and myelination defects in all white matter tracts of the CNS. Furthermore, Cx30/Cx47 double-deficient mice exhibited a decreased number of oligodendrocytes, severe astrogliosis, and microglial activation in white matter tracts. Although less affected concerning motor impairment, surviving double-knock-out (KO) mice showed behavioral alterations in the open field and in the rotarod task. Vacuole formation and thinner myelin sheaths were evident also with adult surviving double-KO mice. Since interastrocytic coupling due to Cx43 expression and interoligodendrocytic coupling because of Cx32 expression are still maintained, Cx30/Cx47 double-deficient mice demonstrate the functional role of both connexins for interastrocytic, interoligodendrocytic, and panglial coupling, and show that both connexins are required for maintenance of myelin.
Keywords:2',3'-Cyclic-Nucleotide Phosphodiesterases, Actins, Age Factors, Basic Helix-Loop-Helix Transcription Factors, Biophysics, Central Nervous System, Connexins, Developmental Gene Expression Regulation, Electric Stimulation, Exploratory Behavior, Gap Junctions, Glial Fibrillary Acidic Protein, Green Fluorescent Proteins, Kaplan-Meier Estimate, Knockout Mice, Maze Learning, Motor Activity, Myelin Sheath, Nerve Tissue Proteins, Neuroglia, Newborn Animals, Nonparametric Statistics, Oligodendroglia, Patch-Clamp Techniques, Psychomotor Performance, Psychophysiologic Habituation, Recognition (Psychology), RNA, Messenger, Silver Staining, Transmission Electron Microscopy, Animals, Mice
Source:Journal of Neuroscience
ISSN:0270-6474
Publisher:Society for Neuroscience (U.S.A.)
Volume:32
Number:22
Page Range:7499-7518
Date:30 May 2012
Official Publication:https://doi.org/10.1523/JNEUROSCI.0392-12.2012
PubMed:View item in PubMed

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