Conditional ablation of Stat3 or Socs3 discloses a dual role for reactive astrocytes after spinal cord injury.
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.
Okada
Seiji
S
Department of Physiology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan.
Nakamura
Masaya
M
Katoh
Hiroyuki
H
Miyao
Tamaki
T
Shimazaki
Takuya
T
Ishii
Ken
K
Yamane
Junichi
J
Yoshimura
Akihiko
A
Iwamoto
Yukihide
Y
Toyama
Yoshiaki
Y
Okano
Hideyuki
H
D000818:Animals; D001253:Astrocytes / Q000502:physiology*; D004195:Disease Models, Animal; D049452:Green Fluorescent Proteins / Q000235:genetics; D007249:Inflammation; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D050796:STAT3 Transcription Factor / Q000172:deficiency* / Q000235:genetics / Q000502:physiology; D015398:Signal Transduction; D013119:Spinal Cord Injuries / Q000235:genetics / Q000503:physiopathology*; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins / Q000172:deficiency* / Q000235:genetics / Q000502:physiology; D014945:Wound Healing
D050796:STAT3 Transcription Factor; C491411:Socs3 protein, mouse; C494087:Stat3 protein, mouse; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D049452:Green Fluorescent Proteins