PMID- 23486965 OWN - NLM STAT- MEDLINE DCOM- 20130506 LR - 20211021 IS - 1529-2401 (Electronic) IS - 0270-6474 (Print) IS - 0270-6474 (Linking) VI - 33 IP - 11 DP - 2013 Mar 13 TI - Oligodendroglial expression of TrkB independently regulates myelination and progenitor cell proliferation. PG - 4947-57 LID - 10.1523/JNEUROSCI.3990-12.2013 [doi] AB - The neurotrophin brain-derived neurotrophic factor (BDNF) has been implicated in regulating CNS myelination. BDNF mutant mice exhibit a hypomyelinating phenotype, and BDNF exerts distinct effects upon oligodendroglial proliferation, differentiation, and myelination in vitro. To investigate the precise influence that BDNF exerts in regulating CNS myelination in vivo, we have generated conditional knock-out mice in which TrkB has been deleted specifically in oligodendrocytes. Deletion of TrkB disrupted normal oligodendrocyte myelination, resulting in a significant reduction in myelin protein expression and myelination of CNS white matter tracts during development. Importantly, conditional knock-out mice exhibited normal numbers of mature oligodendrocytes and normal numbers of myelinated axons; however, myelin thickness was significantly reduced during development. These data indicate that while TrkB expression in oligodendrocytes plays no role in the initial contact with axons, it exerts an important influence in subsequent stages to promote myelin ensheathment. The conditional knock-out mice also exhibited an increased density of oligodendrocyte progenitor cells (OPCs) in CNS white matter tracts. Concordant with these results, in vitro analyses using OPCs subjected to TrkB knockdown also revealed increased OPC proliferation. Our data suggested this effect was dependent upon TrkC and p75 expression. Thus, our data demonstrate that TrkB expression in oligodendroglia exerts a direct effect on oligodendrocytes to promote myelination and an indirect effect upon the OPC population, modifying their proliferative potential. FAU - Wong, Agnes W AU - Wong AW AD - Centre for Neuroscience Research, The University of Melbourne, Victoria 3010, Australia. FAU - Xiao, Junhua AU - Xiao J FAU - Kemper, Dennis AU - Kemper D FAU - Kilpatrick, Trevor J AU - Kilpatrick TJ FAU - Murray, Simon S AU - Murray SS LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - J Neurosci JT - The Journal of neuroscience : the official journal of the Society for Neuroscience JID - 8102140 RN - 0 (Autophagy-Related Proteins) RN - 0 (Intracellular Signaling Peptides and Proteins) RN - 0 (Myelin Basic Protein) RN - 0 (RNA, Messenger) RN - 0 (RNA, Small Interfering) RN - 0 (Rb1cc1 protein, mouse) RN - 0 (Receptor, Nerve Growth Factor) RN - 0 (enhanced green fluorescent protein) RN - 147336-22-9 (Green Fluorescent Proteins) RN - EC 2.7.10.1 (Receptor, Platelet-Derived Growth Factor alpha) RN - EC 2.7.10.1 (Receptor, trkB) RN - EC 2.7.10.1 (Receptor, trkC) RN - EC 2.7.11.1 (Receptor-Interacting Protein Serine-Threonine Kinases) SB - IM MH - Age Factors MH - Analysis of Variance MH - Animals MH - Animals, Newborn MH - Autophagy-Related Proteins MH - Cell Differentiation/genetics MH - *Cell Proliferation MH - Cells, Cultured MH - Central Nervous System/growth & development/metabolism MH - Coculture Techniques MH - Female MH - Ganglia, Spinal/cytology/metabolism MH - Gene Expression Regulation/genetics MH - Green Fluorescent Proteins/genetics MH - Humans MH - Intracellular Signaling Peptides and Proteins/metabolism MH - Male MH - Mice MH - Mice, Inbred C57BL MH - Mice, Transgenic MH - Microscopy, Electron, Transmission MH - Myelin Basic Protein/genetics/metabolism MH - Myelin Sheath/*physiology/ultrastructure MH - Oligodendroglia/*metabolism/ultrastructure MH - RNA, Messenger/metabolism MH - RNA, Small Interfering/genetics/metabolism MH - Rats MH - Rats, Sprague-Dawley MH - Receptor, Nerve Growth Factor/metabolism MH - Receptor, Platelet-Derived Growth Factor alpha/metabolism MH - Receptor, trkB/genetics/*metabolism MH - Receptor, trkC/metabolism MH - Receptor-Interacting Protein Serine-Threonine Kinases/genetics/metabolism MH - Stem Cells/*physiology/ultrastructure MH - Transfection PMC - PMC6619007 EDAT- 2013/03/15 06:00 MHDA- 2013/05/07 06:00 PMCR- 2013/09/13 CRDT- 2013/03/15 06:00 PHST- 2013/03/15 06:00 [entrez] PHST- 2013/03/15 06:00 [pubmed] PHST- 2013/05/07 06:00 [medline] PHST- 2013/09/13 00:00 [pmc-release] AID - 33/11/4947 [pii] AID - 3827133 [pii] AID - 10.1523/JNEUROSCI.3990-12.2013 [doi] PST - ppublish SO - J Neurosci. 2013 Mar 13;33(11):4947-57. doi: 10.1523/JNEUROSCI.3990-12.2013.