Crmp4 deletion promotes recovery from spinal cord injury by neuroprotection and limited scar formation

被引:31
作者
Nagai, Jun [1 ,2 ]
Kitamura, Yoshiteru [1 ]
Owada, Kazuki [1 ]
Yamashita, Naoya [3 ]
Takei, Kohtaro [4 ]
Goshima, Yoshio [3 ]
Ohshima, Toshio [1 ]
机构
[1] Waseda Univ, Grad Sch Adv Sci & Engn, TWIns, Dept Life Sci & Med Biosci, Tokyo 1628480, Japan
[2] Yokohama City Univ, Grad Sch Med, Res Fellow Japan Soc Promot Sci, Yokohama, Kanagawa 2360004, Japan
[3] Yokohama City Univ, Grad Sch Med, Dept Mol Pharmacol & Neurobiol, Yokohama, Kanagawa 2360004, Japan
[4] Yokohama City Univ, Grad Sch Med Life Sci, Dept Med Life Sci, Yokohama, Kanagawa 2360004, Japan
来源
SCIENTIFIC REPORTS | 2015年 / 5卷
关键词
MYELIN-ASSOCIATED INHIBITORS; AXONAL REGENERATION; FUNCTIONAL RECOVERY; CHONDROITINASE ABC; APOPTOSIS; CONTRIBUTE; OUTGROWTH; RHO; DEGENERATION; INFLAMMATION;
D O I
10.1038/srep08269
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
Axonal outgrowth inhibitors and scar formation are two major obstacles to central nervous system (CNS) repair. No target molecule that regulates both axonal growth and scarring has been identified. Here we identified collapsin response mediator protein 4 (CRMP4), a common mediator of inhibitory signals after neural injury, as a crucial factor that contributes to both axonal growth inhibition and scarring after spinal cord injury (SCI). We found increases in the inhibitory and toxic forms of CRMP4 in injured spinal cord. Notably, CRMP4 expression was evident in inflammatory cells as well as in neurons after spinal cord transection. Crmp4(-/-) mice displayed neuroprotection against SCI and reductions in inflammatory response and scar formation. This permissive environment for axonal growth due to CRMP4 deletion restored locomotor activity at an unusually early phase of healing. These results suggest that deletion of CRMP4 is a unique therapeutic strategy that overcomes two obstacles to CNS repair after SCI.
引用
收藏
页数:12
相关论文
共 60 条
[1]   Identification of CRMP4 as a convergent regulator of axon outgrowth inhibition [J].
Alabed, Yazan Z. ;
Pool, Madeline ;
Tone, Stephan Ong ;
Fournier, Alyson E. .
JOURNAL OF NEUROSCIENCE, 2007, 27 (07) :1702-1711
[2]   GSK3β Regulates Myelin-Dependent Axon Outgrowth Inhibition through CRMP4 [J].
Alabed, Yazan Z. ;
Pool, Madeline ;
Tone, Stephan Ong ;
Sutherland, Calum ;
Fournier, Alyson E. .
JOURNAL OF NEUROSCIENCE, 2010, 30 (16) :5635-5643
[3]   PROTEOLYTIC-ENZYMES IN EXPERIMENTAL SPINAL-CORD INJURY [J].
BANIK, NL ;
HOGAN, EL ;
POWERS, JM ;
SMITH, KP .
JOURNAL OF THE NEUROLOGICAL SCIENCES, 1986, 73 (03) :245-256
[4]   Basso mouse scale for locomotion detects differences in recovery after spinal cord in ury in five common mouse strains [J].
Basso, DM ;
Fisher, LC ;
Anderson, AJ ;
Jakeman, LB ;
McTigue, DM ;
Popovich, PG .
JOURNAL OF NEUROTRAUMA, 2006, 23 (05) :635-659
[5]   Review of current evidence for apoptosis after spinal cord injury [J].
Beattie, MS ;
Farooqui, AA ;
Bresnahan, JC .
JOURNAL OF NEUROTRAUMA, 2000, 17 (10) :915-925
[6]   Chondroitinase ABC promotes functional recovery after spinal cord injury [J].
Bradbury, EJ ;
Moon, LDF ;
Popat, RJ ;
King, VR ;
Bennett, GS ;
Patel, PN ;
Fawcett, JW ;
McMahon, SB .
NATURE, 2002, 416 (6881) :636-640
[7]   Manipulating the glial scar: Chondroitinase ABC as a therapy for spinal cord injury [J].
Bradbury, Elizabeth J. ;
Carter, Lucy M. .
BRAIN RESEARCH BULLETIN, 2011, 84 (4-5) :306-316
[8]   Prior exposure to neurotrophins blocks inhibition of axonal regeneration by MAG and myelin via a cAMP-dependent mechanism [J].
Cai, DM ;
Shen, YJ ;
De Bellard, M ;
Tang, S ;
Filbin, MT .
NEURON, 1999, 22 (01) :89-101
[9]   The Yellow Fluorescent Protein (YFP-H) Mouse Reveals Neuroprotection as a Novel Mechanism Underlying Chondroitinase ABC-Mediated Repair after Spinal Cord Injury [J].
Carter, Lucy M. ;
Starkey, Michelle L. ;
Akrimi, Sonia F. ;
Davies, Meirion ;
McMahon, Stephen B. ;
Bradbury, Elizabeth J. .
JOURNAL OF NEUROSCIENCE, 2008, 28 (52) :14107-14120
[10]   Distinct priming kinases contribute to differential regulation of collapsin response mediator proteins by glycogen synthase kinase-3 in vivo [J].
Cole, Adam R. ;
Causeret, Frederic ;
Yadirgi, Gokhan ;
Hastie, C. James ;
McLauchlan, Hilary ;
McManus, Edward J. ;
Hernandez, Felix ;
Eickholt, Britta J. ;
Nikolic, Margareta ;
Sutherland, Calum .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2006, 281 (24) :16591-16598