Conditional ablation of Stat3 or Socs3 discloses a dual role for reactive astrocytes after spinal cord injury

Seiji Okada, Masaya Nakamura, Hiroyuki Katoh, Tamaki Miyao, Takuya Shimazaki, Ken Ishii, Junichi Yamane, Akihiko Yoshimura, Yukihide Iwamoto, Yoshiaki Toyama, Hideyuki Okano

Research output: Contribution to journalArticle

552 Citations (Scopus)

Abstract

In the injured central nervous system (CNS), reactive astrocytes form a glial scar and are considered to be detrimental for axonal regeneration, but their function remains elusive. Here we show that reactive astrocytes have a crucial role in wound healing and functional recovery by using mice with a selective deletion of the protein signal transducer and activator of transcription 3 (Stat3) or the protein suppressor of cytokine signaling 3 (Socs3) under the control of the Nes promoter-enhancer (Nes-Stat3-/-, Nes-Socs3-/-). Reactive astrocytes in Nes-Stat3-/- mice showed limited migration and resulted in markedly widespread infiltration of inflammatory cells, neural disruption and demyelination with severe motor deficits after contusive spinal cord injury (SCI). On the contrary, we observed rapid migration of reactive astrocytes to seclude inflammatory cells, enhanced contraction of lesion area and notable improvement in functional recovery in Nes-Socs3-/- mice. These results suggest that Stat3 is a key regulator of reactive astrocytes in the healing process after SCI, providing a potential target for intervention in the treatment of CNS injury.

Original languageEnglish
Pages (from-to)829-834
Number of pages6
JournalNature Medicine
Volume12
Issue number7
DOIs
Publication statusPublished - 2006 Jul

Fingerprint

STAT3 Transcription Factor
Ablation
Spinal Cord Injuries
Astrocytes
Cytokines
Neurology
Central Nervous System
Suppressor of Cytokine Signaling Proteins
Nervous System Trauma
Recovery
Demyelinating Diseases
Infiltration
Neuroglia
Wound Healing
Cicatrix
Regeneration
Proteins

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Conditional ablation of Stat3 or Socs3 discloses a dual role for reactive astrocytes after spinal cord injury. / Okada, Seiji; Nakamura, Masaya; Katoh, Hiroyuki; Miyao, Tamaki; Shimazaki, Takuya; Ishii, Ken; Yamane, Junichi; Yoshimura, Akihiko; Iwamoto, Yukihide; Toyama, Yoshiaki; Okano, Hideyuki.

In: Nature Medicine, Vol. 12, No. 7, 07.2006, p. 829-834.

Research output: Contribution to journalArticle

Okada, Seiji ; Nakamura, Masaya ; Katoh, Hiroyuki ; Miyao, Tamaki ; Shimazaki, Takuya ; Ishii, Ken ; Yamane, Junichi ; Yoshimura, Akihiko ; Iwamoto, Yukihide ; Toyama, Yoshiaki ; Okano, Hideyuki. / Conditional ablation of Stat3 or Socs3 discloses a dual role for reactive astrocytes after spinal cord injury. In: Nature Medicine. 2006 ; Vol. 12, No. 7. pp. 829-834.
@article{b0f53c7fac44421f9444170909349672,
title = "Conditional ablation of Stat3 or Socs3 discloses a dual role for reactive astrocytes after spinal cord injury",
abstract = "In the injured central nervous system (CNS), reactive astrocytes form a glial scar and are considered to be detrimental for axonal regeneration, but their function remains elusive. Here we show that reactive astrocytes have a crucial role in wound healing and functional recovery by using mice with a selective deletion of the protein signal transducer and activator of transcription 3 (Stat3) or the protein suppressor of cytokine signaling 3 (Socs3) under the control of the Nes promoter-enhancer (Nes-Stat3-/-, Nes-Socs3-/-). Reactive astrocytes in Nes-Stat3-/- mice showed limited migration and resulted in markedly widespread infiltration of inflammatory cells, neural disruption and demyelination with severe motor deficits after contusive spinal cord injury (SCI). On the contrary, we observed rapid migration of reactive astrocytes to seclude inflammatory cells, enhanced contraction of lesion area and notable improvement in functional recovery in Nes-Socs3-/- mice. These results suggest that Stat3 is a key regulator of reactive astrocytes in the healing process after SCI, providing a potential target for intervention in the treatment of CNS injury.",
author = "Seiji Okada and Masaya Nakamura and Hiroyuki Katoh and Tamaki Miyao and Takuya Shimazaki and Ken Ishii and Junichi Yamane and Akihiko Yoshimura and Yukihide Iwamoto and Yoshiaki Toyama and Hideyuki Okano",
year = "2006",
month = "7",
doi = "10.1038/nm1425",
language = "English",
volume = "12",
pages = "829--834",
journal = "Nature Medicine",
issn = "1078-8956",
publisher = "Nature Publishing Group",
number = "7",

}

TY - JOUR

T1 - Conditional ablation of Stat3 or Socs3 discloses a dual role for reactive astrocytes after spinal cord injury

AU - Okada, Seiji

AU - Nakamura, Masaya

AU - Katoh, Hiroyuki

AU - Miyao, Tamaki

AU - Shimazaki, Takuya

AU - Ishii, Ken

AU - Yamane, Junichi

AU - Yoshimura, Akihiko

AU - Iwamoto, Yukihide

AU - Toyama, Yoshiaki

AU - Okano, Hideyuki

PY - 2006/7

Y1 - 2006/7

N2 - In the injured central nervous system (CNS), reactive astrocytes form a glial scar and are considered to be detrimental for axonal regeneration, but their function remains elusive. Here we show that reactive astrocytes have a crucial role in wound healing and functional recovery by using mice with a selective deletion of the protein signal transducer and activator of transcription 3 (Stat3) or the protein suppressor of cytokine signaling 3 (Socs3) under the control of the Nes promoter-enhancer (Nes-Stat3-/-, Nes-Socs3-/-). Reactive astrocytes in Nes-Stat3-/- mice showed limited migration and resulted in markedly widespread infiltration of inflammatory cells, neural disruption and demyelination with severe motor deficits after contusive spinal cord injury (SCI). On the contrary, we observed rapid migration of reactive astrocytes to seclude inflammatory cells, enhanced contraction of lesion area and notable improvement in functional recovery in Nes-Socs3-/- mice. These results suggest that Stat3 is a key regulator of reactive astrocytes in the healing process after SCI, providing a potential target for intervention in the treatment of CNS injury.

AB - In the injured central nervous system (CNS), reactive astrocytes form a glial scar and are considered to be detrimental for axonal regeneration, but their function remains elusive. Here we show that reactive astrocytes have a crucial role in wound healing and functional recovery by using mice with a selective deletion of the protein signal transducer and activator of transcription 3 (Stat3) or the protein suppressor of cytokine signaling 3 (Socs3) under the control of the Nes promoter-enhancer (Nes-Stat3-/-, Nes-Socs3-/-). Reactive astrocytes in Nes-Stat3-/- mice showed limited migration and resulted in markedly widespread infiltration of inflammatory cells, neural disruption and demyelination with severe motor deficits after contusive spinal cord injury (SCI). On the contrary, we observed rapid migration of reactive astrocytes to seclude inflammatory cells, enhanced contraction of lesion area and notable improvement in functional recovery in Nes-Socs3-/- mice. These results suggest that Stat3 is a key regulator of reactive astrocytes in the healing process after SCI, providing a potential target for intervention in the treatment of CNS injury.

UR - http://www.scopus.com/inward/record.url?scp=33745919498&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33745919498&partnerID=8YFLogxK

U2 - 10.1038/nm1425

DO - 10.1038/nm1425

M3 - Article

VL - 12

SP - 829

EP - 834

JO - Nature Medicine

JF - Nature Medicine

SN - 1078-8956

IS - 7

ER -