Dynamic CCN3 expression in the murine CNS does not confer essential roles in myelination or remyelination

被引:20
作者
Gallardo, Nira de la Vega [1 ]
Penalva, Rosana [1 ]
Dittmer, Marie [1 ]
Naughton, Michelle [1 ]
Falconer, John [1 ]
Moffat, Jill [1 ]
de la Fuente, Alerie G. [1 ]
Hombrebueno, Jose R. [2 ]
Lin, Zhiyong [3 ]
Perbal, Bernard [4 ]
Ingram, Rebecca J. [1 ]
Evergren, Emma [5 ]
Fitzgerald, Denise C. [1 ]
机构
[1] Queens Univ Belfast, Wellcome Wolfson Inst Expt Med, Belfast BT9 7BL, Antrim, North Ireland
[2] Univ Birmingham, Inst Inflammat & Ageing, Birmingham B15 2TT, W Midlands, England
[3] Emory Univ, Dept Med, Cardiol Div, Sch Med, Atlanta, GA 30322 USA
[4] Int CCN Soc, F-13001 Marseille, France
[5] Queens Univ Belfast, Patrick G Johnston Ctr Canc Res, Belfast BT9 7AE, Antrim, North Ireland
基金
英国惠康基金; 英国生物技术与生命科学研究理事会;
关键词
CCN3; myelin; oligodendrocyte; OPC; remyelination; CENTRAL-NERVOUS-SYSTEM; MULTIPLE-SCLEROSIS; DISEASE STAGES; SCHWANN-CELLS; GROWTH; OLIGODENDROCYTES; GENE; NOV; PROTEIN; RNA;
D O I
10.1073/pnas.1922089117
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
CCN3 is a matricellular protein that promotes oligodendrocyte progenitor cell differentiation and myelination in vitro and ex vivo. CCN3 is therefore a candidate of interest in central nervous system (CNS) myelination and remyelination, and we sought to investigate the expression and role of CCN3 during these processes. We found CCN3 to be expressed predominantly by neurons in distinct areas of the CNS, primarily the cerebral cortex, hippocampus, amygdala, suprachiasmatic nuclei, anterior olfactory nuclei, and spinal cord gray matter. CCN3 was transiently up-regulated following demyelination in the brain of cuprizone-fed mice and spinal cord lesions of mice injected with lysolecithin. However, CCN3(-/-) mice did not exhibit significantly different numbers of oligodendroglia or differentiated oligodendrocytes in the healthy or remyelinating CNS, compared to WT controls. These results suggest that despite robust and dynamic expression in the CNS, CCN3 is not required for efficient myelination or remyelination in the murine CNS in vivo.
引用
收藏
页码:18018 / 18028
页数:11
相关论文
共 50 条
[1]  
Burren CP, 1999, J CLIN ENDOCR METAB, V84, P1096
[2]   Functions and mechanisms of action of CCN matricellular proteins [J].
Chen, Chih-Chiun ;
Lau, Lester F. .
INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY, 2009, 41 (04) :771-783
[3]  
Chevalier G, 1998, AM J PATHOL, V152, P1563
[4]   NG2-expressing glial progenitor cells: an abundant and widespread population of cycling cells in the adult rat CNS [J].
Dawson, MRL ;
Polito, A ;
Levine, JM ;
Reynolds, R .
MOLECULAR AND CELLULAR NEUROSCIENCE, 2003, 24 (02) :476-488
[5]   Characterization of a murine mixed neuron-glia model and cellular responses to regulatory T cell-derived factors [J].
Dittmer, Marie ;
Young, Andrew ;
O'Hagan, Thomas ;
Eleftheriadis, George ;
Bankhead, Peter ;
Dombrowski, Yvonne ;
Medina, Reinhold J. ;
Fitzgerald, Denise C. .
MOLECULAR BRAIN, 2018, 11
[6]   Regulatory T cells promote myelin regeneration in the central nervous system [J].
Dombrowski, Yvonne ;
O'Hagan, Thomas ;
Dittmer, Marie ;
Penalva, Rosana ;
Mayoral, Sonia R. ;
Bankhead, Peter ;
Fleville, Samara ;
Eleftheriadis, George ;
Zhao, Chao ;
Naughton, Michelle ;
Hassan, Rachel ;
Moffat, Jill ;
Falconer, John ;
Boyd, Amanda ;
Hamilton, Peter ;
Allen, Ingrid V. ;
Kissenpfennig, Adrien ;
Moynagh, Paul N. ;
Evergren, Emma ;
Perbal, Bernard ;
Williams, Anna C. ;
Ingram, Rebecca J. ;
Chan, Jonah R. ;
Franklin, Robin J. M. ;
Fitzgerald, Denise C. .
NATURE NEUROSCIENCE, 2017, 20 (05) :674-+
[7]   Neuronal CTGF/CCN2 negatively regulates myelination in a mouse model of tuberous sclerosis complex [J].
Ercan, Ebru ;
Han, Juliette M. ;
Di Nardo, Alessia ;
Winden, Kellen ;
Han, Min-Joon ;
Hoyo, Leonie ;
Saffari, Afshin ;
Leask, Andrew ;
Geschwind, Daniel H. ;
Sahin, Mustafa .
JOURNAL OF EXPERIMENTAL MEDICINE, 2017, 214 (03) :681-697
[8]  
FORAN DR, 1992, J NEUROSCI, V12, P4890
[9]   CCN3 (NOV) interacts with connexin43 in C6 glioma cells - Possible mechanism of connexin-mediated growth suppression [J].
Fu, CT ;
Bechberger, JF ;
Ozog, MA ;
Perbal, B ;
Naus, CC .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2004, 279 (35) :36943-36950
[10]   Glycolytic oligodendrocytes maintain myelin and long-term axonal integrity [J].
Fuenfschilling, Ursula ;
Supplie, Lotti M. ;
Mahad, Don ;
Boretius, Susann ;
Saab, Aiman S. ;
Edgar, Julia ;
Brinkmann, Bastian G. ;
Kassmann, Celia M. ;
Tzvetanova, Iva D. ;
Moebius, Wiebke ;
Diaz, Francisca ;
Meijer, Dies ;
Suter, Ueli ;
Hamprecht, Bernd ;
Sereda, Michael W. ;
Moraes, Carlos T. ;
Frahm, Jens ;
Goebbels, Sandra ;
Nave, Klaus-Armin .
NATURE, 2012, 485 (7399) :517-U130