Locomotor recovery following contusive spinal cord injury does not require oligodendrocyte remyelination

被引:81
作者
Duncan, Greg J. [1 ,2 ]
Manesh, Sohrab B. [1 ,3 ]
Hilton, Brett J. [1 ,2 ,6 ]
Assinck, Peggy [1 ,3 ]
Liu, Jie [1 ]
Moulson, Aaron [1 ,2 ]
Plemel, Jason R. [4 ]
Tetzlaff, Wolfram [1 ,2 ,5 ]
机构
[1] Univ British Columbia, ICORD, 818 West 10th Ave, Vancouver, BC V5Z 1M9, Canada
[2] Univ British Columbia, Dept Zool, 4200-6270 Univ Blvd, Vancouver, BC V6T 1Z4, Canada
[3] Univ British Columbia, Grad Program Neurosci, 3402-2215 Wesbrook Mall, Vancouver, BC V6T 1Z3, Canada
[4] Univ Calgary, Hotchkiss Brain Inst, Dept Clin Neurosci, 3330 Hosp Dr NW, Calgary, AB T2N 4N1, Canada
[5] Univ British Columbia, Dept Surg, 2775 Laurel St, Vancouver, BC V5Z 1M9, Canada
[6] DZNE, Sigmund Freud Str 27, D-53127 Bonn, Germany
关键词
PDGF ALPHA-RECEPTOR; FUNCTIONAL RECOVERY; EXTENSIVE REMYELINATION; CHRONIC DEMYELINATION; AXONAL PHYSIOLOGY; REGULATORY FACTOR; NG2; PROTEOGLYCAN; CELLS; MYELIN; CONDUCTION;
D O I
10.1038/s41467-018-05473-1
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
Remyelination occurs after spinal cord injury (SCI) but its functional relevance is unclear. We assessed the necessity of myelin regulatory factor (Myrf) in remyelination after contusive SCI by deleting the gene from platelet-derived growth factor receptor alpha positive (PDGFR alpha-positive) oligodendrocyte progenitor cells (OPCs) in mice prior to SCI. While OPC proliferation and density are not altered by Myrf inducible knockout after SCI, the accumulation of new oligodendrocytes is largely prevented. This greatly inhibits myelin regeneration, resulting in a 44% reduction in myelinated axons at the lesion epicenter. However, spontaneous locomotor recovery after SCI is not altered by remyelination failure. In controls with functional MYRF, locomotor recovery precedes the onset of most oligodendrocyte myelin regeneration. Collectively, these data demonstrate that MYRF expression in PDGFR alpha-positive cell derived oligodendrocytes is indispensable for myelin regeneration following contusive SCI but that oligodendrocyte remyelination is not required for spontaneous recovery of stepping.
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页数:16
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