Authors
Bin Sun, Li Sun, Lixiang Zhang, Xinyu Xue, Qiuyan Tian, Lei Wu, Mei Li, Jian Huang, Hong Ni, Lixiao Xu, Chenxi Feng, Jing Ren, Hongliang Huo, Xia Zhang, Xing Feng, Wenhao Zhou, Wanliang Guo, Yaobo Liu, Rong Ju, Zhenlang Lin, Xiaofeng Yang, Xin Ding
Published in
Genes & diseases. Volume 13. Issue 5. Pages 102000. Epub Dec 22, 2025.
Abstract
Spontaneous recovery following an ischemic stroke is often limited, largely attributed to age-related decline in neuroplasticity. To overcome this, we demonstrated that ectopic expression of a cocktail of transcriptional factors (Oct4, Sox2, and Klf4, referred to as OSKTFs) reset developmental decline of epigenetic signatures in adult corticospinal neurons, without affecting their spinal projection patterns and function in controlling skilled locomotion. Corticospinal expression of OSKTFs had moderate effects on promoting collateral sprouting of the corticospinal tract axons and recovery of skilled motor function following a photothrombotic stroke. When combined with task-dependent rehabilitative training, OSKTFs treatment significantly enhanced its efficacy, suggesting that rejuvenating corticospinal neurons substantially amplifies the beneficial outcomes of rehabilitative training. Mechanistically, pharmacological perturbations and intersectional chemogenetic inhibition establish that both axon sprouting and functional recovery require mTOR activation and are mediated by newly sprouted corticospinal tract axons. Together, these findings identify a novel strategy to rejuvenate adult corticospinal neurons, which improves the otherwise modest benefits typically gained from rehabilitative training after traumatic brain injuries.
PMID:
42339206
Bibliographic data and abstract were imported from PubMed on 24 Jun 2026.
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