Knockdown of polypyrimidine tract binding protein facilitates motor function recovery after spinal cord injury

作     者：Ri-Yun Yang Rui Chai Jing-Ying Pan Jing-Yin Bao Pan-Hui Xia Yan-Kai Wang Ying Chen Yi Li Jian Wu Gang Chen Ri-Yun Yang;Rui Chai;Jing-Ying Pan;Jing-Yin Bao;Pan-Hui Xia;Yan-Kai Wang;Ying Chen;Yi Li;Jian Wu;Gang Chen

作者机构：Department of Histology and EmbryologyMedical School of Nantong UniversityNantongJiangsu ProvinceChina Key Laboratory of Neuroregeneration of Jiangsu Province and the Ministry of EducationCo-innovation Center of NeuroregenerationNantong UniversityNantongJiangsu ProvinceChina Center for Basic Medical ResearchMedical School of Nantong UniversityNantongJiangsu ProvinceChina Department of AnesthesiologyAffiliated Hospital of Nantong UniversityNantongJiangsu ProvinceChina 

出 版 物：《Neural Regeneration Research》 (中国神经再生研究（英文版）)

年 卷 期：2023年第18卷第2期

页      面：396-403页

核心收录：

学科分类：0710[理学-生物学] 1002[医学-临床医学] 1001[医学-基础医学(可授医学、理学学位)] 10[医学] 

基　　金：supported by the National Natural Science Foundation of China,Nos.82101455(to RYY),31872773(to GC),82001168(to JYP) the Key Research and Development Program(Social Development)of Jiangsu Province,No.BE2020667(to GC) the Foundation of Jiangsu Province,333 Project High-level Talents",No.BRA2020076(to GC) the Nantong Civic Science and Technology Project of China,No.JC2020028(to RYY) the Natural Science Research of Jiangsu Higher Education Institutions of China,No.19KJB310012(to RYY) Priority Academic Program Development of Jiangsu Higher Education Institutions(PAPD)。 

主　　题：antisense oligonucleotides astrocytes glial scar motoneuron-like cells motor function neurogenesis neuron-like cells polypyrimidine tract binding protein short hairpin RNAs spinal cord repair 

摘      要：After spinal cord injury(SCI),a fibroblast-and microglia-mediated fibrotic scar is formed in the lesion core,and a glial scar is formed around the fibrotic scar as a res ult of the activation and proliferation of astrocytes.Simultaneously,a large number of neuro ns are lost in the injured area.Regulating the dense glial scar and re plenishing neurons in the injured area are essential for SCI repair.Polypyrimidine tra ct binding protein(PTB),known as an RNA-binding protein,plays a key role in neurogenesis.Here,we utilized short hairpin RNAs(shRNAs)and antisense oligonucleotides(ASOs)to knock down PTB expression.We found that reactive spinal astrocytes from mice were directly reprogrammed into motoneuron-like cells by PTB downregulation in vitro.In a mouse model of compressioninduced SCI,adeno-associated viral shRNA-mediated PTB knockdown replenished motoneuron-like cells around the injured area.Basso Mouse Scale scores and forced swim,inclined plate,cold allodynia,and hot plate tests showed that PTB knockdown promoted motor function recovery in mice but did not improve sensory perception after SCI.Furthermore,ASO-mediated PTB knockdown improved motor function resto ration by not only replenishing motoneuron-like cells around the injured area but also by modestly reducing the density of the glial scar without disrupting its overall structure.Together,these findings suggest that PTB knockdown may be a promising therapeutic strategy to promote motor function recovery during spinal cord repair.