Effects of rapamycin and chemogenetic silencing on CST sprouting and functional recovery with combined treatment (IMAGE)

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Effects of rapamycin and chemogenetic silencing on CST sprouting and functional recovery with combined treatment

Caption

(A) The timeline of the experimental design of mTOR inactivation with OSKTFs treatment and rehabilitation. (B, C) Performance of single pellet retrieval (B) and irregular ladder walking (C) tasks at different time points after stroke in OSKTFs mice treated with saline (n = 12), with doxycycline (Dox) and rehabilitative training (n = 12), or with Dox/rapamycin and rehabilitative training (n = 12). Blue ∗∗P < 0.01 and ∗P < 0.05 (Rehab + OSKTFs versus saline); n.s., no statistical significance (Rehab + OSKTFs & rapamycin vs saline); repeated measures of two-way ANOVA followed by the Bonferroni correction. (D–G) Representative transverse images with high-magnitude ones of the cervical spinal cord showing CST axons (D–F), along with quantification of the CST axon sprouting indexes (G) at different distances to the midline in OSKTFs stroke mice treated with saline (n = 5), rehabilitative training with Dox (n = 5), or rehabilitative training with Dox and rapamycin (n = 5). ∗∗P < 0.01 and ∗P < 0.05; one-way ANOVA followed by the Bonferroni correction. Scale bar: 500 μm. (H) The timeline of the experimental design of chemogenetic inactivation of sprouted corticospinal neurons with OSKTFs treatment and rehabilitation. (I, J) Schematic drawing of experimental design (I) and a representative image (J) showing hM4Di-mCitrine or GFP expression in corticospinal neurons with midline-crossing collateral sprouting. Scale bar: 500 μm. (K, L) Performance of single pellet retrieval (K) and irregular ladder walking (L) tasks in OSKTFsDox animals with intersectional GFP (n = 8) or hM4Di-mCitrine (n = 8) expression before and 1 h after CNO. n.s., no statistical significance; ∗∗P < 0.01; paired t-test.

Credit

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

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