Targeted expression of anti-apoptotic protein p35 in oligodendrocytes reduces delayed demyelination and functional impairment after spinal cord injury.
Functional impairment after spinal cord injury (SCI) is attributed to neuronal cell necrosis death and axonotmesis, with further worsening caused by the accompanying apoptosis of myelin-forming oligodendrocytes (OLGs). However, it is unclear as to how much OLG apoptosis contributes to functional impairment. To address this issue, we used transgenic mice characterized by the targeted expression of p35, a broad-spectrum caspase inhibitor, in OLGs using the cre/loxP system (referred to as cre/p35 transgenic mice). In this study, we examined the motor function and histopathologic changes after a contusive thoracic spinal cord injury in the cre/p35 transgenic mice. A larger number of OLGs and a lesser extent of demyelination were observed after SCI in the cre/p35 transgenic mice than in the control cre mice, which did not carry the p35 transgene. Furthermore, the motor function of the hindlimbs recovered to a significantly better degree in the cre/p35 transgenic mice than in the control cre mice. Thus, the inhibition of OLG apoptosis decreased the extent of functional impairment after SCI. These findings suggest that the inhibition of OLG apoptosis may be a potential treatment for SCI.
Tamura
Mutsuhiro
M
Department of Orthopaedic Surgery, Keio University School of Medicine, Tokyo, Japan.
Nakamura
Masaya
M
Ogawa
Yuto
Y
Toyama
Yoshiaki
Y
Miura
Masayuki
M
Okano
Hideyuki
H
D000818:Animals; D017209:Apoptosis / Q000235:genetics*; D003711:Demyelinating Diseases / Q000235:genetics / Q000378:metabolism / Q000628:therapy; D004195:Disease Models, Animal; D005260:Female; D005786:Gene Expression Regulation / Q000235:genetics; D018390:Gene Targeting / Q000379:methods; D015316:Genetic Therapy / Q000379:methods; D051379:Mice; D008822:Mice, Transgenic; D009416:Nerve Regeneration / Q000235:genetics*; D009836:Oligodendroglia / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D010770:Phosphotransferases / Q000096:biosynthesis* / Q000235:genetics*; D020127:Recovery of Function / Q000235:genetics; D013119:Spinal Cord Injuries / Q000235:genetics / Q000378:metabolism* / Q000628:therapy; D013997:Time Factors; D016896:Treatment Outcome; D014855:Wallerian Degeneration / Q000235:genetics / Q000378:metabolism / Q000628:therapy
C492236:Cdk5r1 protein, mouse; D010770:Phosphotransferases