Targeted expression of anti-apoptotic protein p35 in oligodendrocytes reduces delayed demyelination and functional impairment after spinal cord injury

Mutsuhiro Tamura, Masaya Nakamura, Yuto Ogawa, Yoshiaki Toyama, Masayuki Miura, Hideyuki Okano

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

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 ere 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.

Original languageEnglish
Pages (from-to)312-321
Number of pages10
JournalGLIA
Volume51
Issue number4
DOIs
Publication statusPublished - 2005 Sep

Fingerprint

Apoptosis Regulatory Proteins
Oligodendroglia
Demyelinating Diseases
Spinal Cord Injuries
Transgenic Mice
Apoptosis
Nervous System Trauma
Thoracic Injuries
Caspase Inhibitors
Hindlimb
Myelin Sheath
Transgenes
Cell Death
Necrosis

Keywords

  • Apoptosis
  • Caspase
  • Functional recovery
  • Oligodendrocyte
  • Spinal cord injury

ASJC Scopus subject areas

  • Immunology

Cite this

Targeted expression of anti-apoptotic protein p35 in oligodendrocytes reduces delayed demyelination and functional impairment after spinal cord injury. / Tamura, Mutsuhiro; Nakamura, Masaya; Ogawa, Yuto; Toyama, Yoshiaki; Miura, Masayuki; Okano, Hideyuki.

In: GLIA, Vol. 51, No. 4, 09.2005, p. 312-321.

Research output: Contribution to journalArticle

@article{0558ab1971744456a0102cb93c5528e5,
title = "Targeted expression of anti-apoptotic protein p35 in oligodendrocytes reduces delayed demyelination and functional impairment after spinal cord injury",
abstract = "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 ere 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.",
keywords = "Apoptosis, Caspase, Functional recovery, Oligodendrocyte, Spinal cord injury",
author = "Mutsuhiro Tamura and Masaya Nakamura and Yuto Ogawa and Yoshiaki Toyama and Masayuki Miura and Hideyuki Okano",
year = "2005",
month = "9",
doi = "10.1002/glia.20212",
language = "English",
volume = "51",
pages = "312--321",
journal = "GLIA",
issn = "0894-1491",
publisher = "John Wiley and Sons Inc.",
number = "4",

}

TY - JOUR

T1 - Targeted expression of anti-apoptotic protein p35 in oligodendrocytes reduces delayed demyelination and functional impairment after spinal cord injury

AU - Tamura, Mutsuhiro

AU - Nakamura, Masaya

AU - Ogawa, Yuto

AU - Toyama, Yoshiaki

AU - Miura, Masayuki

AU - Okano, Hideyuki

PY - 2005/9

Y1 - 2005/9

N2 - 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 ere 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.

AB - 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 ere 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.

KW - Apoptosis

KW - Caspase

KW - Functional recovery

KW - Oligodendrocyte

KW - Spinal cord injury

UR - http://www.scopus.com/inward/record.url?scp=25444469096&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=25444469096&partnerID=8YFLogxK

U2 - 10.1002/glia.20212

DO - 10.1002/glia.20212

M3 - Article

VL - 51

SP - 312

EP - 321

JO - GLIA

JF - GLIA

SN - 0894-1491

IS - 4

ER -