Related Experiment Video
Updated: Aug 13, 2026
Induction of Complete Transection-Type Spinal Cord Injury in Mice
Published on: May 6, 2020
Activation of JAK/STAT signalling in neurons following spinal cord injury in mice
Katsuaki Yamauchi1, Koji Osuka, Masakazu Takayasu
1Department of Neurosurgery, Nagoya University, Graduate School of Medicine, Nagoya, Japan.
Abstract:
The Janus kinase (JAK)/signal transducer and activator of transcription (STAT) signalling pathway is one of the most important in transducing signals from the cell surface to the nucleus in response to cytokines. In the present study, we investigated chronological alteration and cellular location of JAK1, STAT3, phosphorylated (p)-Tyr1022/1023-JAK1, p-Tyr705-STAT3, and interleukin-6 (IL-6) following spinal cord injury (SCI) in mice. Western blot analysis showed JAK1 to be significantly phosphorylated at Tyr1022/1023 from 6 h after SCI, peaking at 12 h and gradually decreasing thereafter, accompanied by phosphorylation of STAT3 at Tyr705 with a similar time course. ELISA analysis showed the concentration of IL-6 in injured spinal cord to also significantly increase from 3 h after SCI, peaking at 12 h, then gradually decreasing. Immunohistochemistry revealed p-Tyr1022/1023-JAK1, p-Tyr705-STAT3, and IL-6 to be mainly expressed in neurons of the anterior horns at 12 h after SCI. Pretreatment with a JAK inhibitor, AG-490, suppressed phosphorylation of JAK1 and STAT3 at 12 h after SCI, reducing recovery of motor functions. These findings suggest that SCI at the acute stage produces IL-6 mainly in neurons of the injured spinal cord, which activates the JAK/STAT pathway, and that this pathway may be involved with neuronal response to SCI.
Insights
Spinal cord injury (SCI) activates the Janus kinase (JAK)/signal transducer and activator of transcription (STAT) pathway, involving interleukin-6 (IL-6) produced by neurons. Inhibiting this pathway impairs motor function recovery after SCI.
Area of Science:
- Neuroscience
- Cellular Biology
- Biochemistry
Background:
- The Janus kinase (JAK)/signal transducer and activator of transcription (STAT) pathway is crucial for cellular responses to cytokines.
- Understanding the role of this pathway in spinal cord injury (SCI) is vital for developing therapeutic strategies.
Purpose of the Study:
- To investigate the temporal changes and cellular localization of key components of the JAK/STAT pathway (JAK1, STAT3, IL-6) following SCI in a mouse model.
- To determine the involvement of the JAK/STAT pathway in the neuronal response to acute SCI and its impact on motor function.
Main Methods:
- Western blot analysis to assess protein phosphorylation levels of JAK1 and STAT3.
- Enzyme-linked immunosorbent assay (ELISA) to quantify IL-6 concentration.
- Immunohistochemistry to determine the cellular expression of phosphorylated JAK1, STAT3, and IL-6.
- Administration of a JAK inhibitor (AG-490) to evaluate its effect on SCI outcomes.
Main Results:
- SCI induced significant phosphorylation of JAK1 and STAT3, peaking at 12 hours post-injury.
- Interleukin-6 (IL-6) levels increased significantly from 3 hours post-SCI, peaking at 12 hours.
- Phosphorylated JAK1, STAT3, and IL-6 were primarily localized in neurons of the anterior horns at 12 hours post-SCI.
- JAK inhibitor pretreatment suppressed JAK/STAT activation and reduced motor function recovery.
Conclusions:
- Acute SCI triggers IL-6 production in spinal cord neurons, activating the JAK/STAT signaling pathway.
- The JAK/STAT pathway plays a significant role in the neuronal response to acute SCI.
- Targeting the JAK/STAT pathway may offer a therapeutic approach for improving motor function after SCI.
