DOI: 10.1002/ame2.12545
Effect of in vivo reprogramming of astrocytes combined with exercise training on neurorepair in rats with spinal cord injury
Zuliyaer Talifu
Xin Xu
Huayong Du
Zehui Li
Xiaoxin Wang
Chunjia Zhang
Yunzhu Pan
Han Ke
Wubo Liu
Feng Gao
Degang Yang
Yingli Jing
Yan Yu
Liangjie Du
Jianjun Li
Abstract：Background: The inability of damaged neurons to regenerate and of axons to establish new functional connections leads to permanent functional deficits after spinal cord injury (SCI). Although astrocyte reprogramming holds promise for neurorepair in various disease models, it is not sufficient on its own to achieve significant functional recovery.
Methods: A rat SCI model was established using a spinal cord impactor. Seven days post-surgery, adeno-associated virus were injected to overexpress the transcription factors NeuroD1 and Neurogenin-2 (Ngn2) in the spinal cord. The rats were then trained to walk on a weight-supported treadmill for 4 weeks, starting 14 days after modeling. The effects of these interventions on motor and sensory functions, as well as spinal cord tissue repair, were subsequently evaluated.
Results: The combination of NeuroD1 and Ngn2 overexpression with weight-supported exercise training significantly improved gait compared to either intervention alone. The group receiving the combined intervention exhibited enhanced sensitivity in sensory assessments. Immunofluorescence analysis revealed increased colocalization of astrocytes and microtubule-associated protein 2-positive neurons in the injury area. These effects were more pronounced than those observed with spinal cord tissue repair alone. Additionally, the combined intervention significantly reduced glial scarring and the size of the injury area.
Conclusion: Exercise intervention enhances the reprogramming effects of astrocytes and restores motor function, yielding better results than either intervention alone.
Keywords：astrocyteexercise trainingfunctional recoveryreprogrammingspinal cord injury
Publication Date：2025-04-30
Online Publishing Date：2025-08-15(First online date of this platform, not the publication date of the document)
Pages：11( 595-605 )