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. 2021 Mar 26;13:612856. doi: 10.3389/fnagi.2021.612856

Figure 7.

Figure 7

Direct conversion of astrocytes to neurons improved functional recovery after stroke. Functional and behavioral tests were performed different days after stroke to evaluate the therapeutic benefits of the direct conversion therapy using ND1 transduction. (A) The rotarod test was performed 21 days after stroke to measure the motor function of stroke animals. Stroke animals disabled a disability in balancing on the rotarod beam, their time spent on the beam was significantly shorter than sham control mice. ND1 conversion treatment noticeably improved the motor function of maintaining on the beam with a longer time. N = 6/group, two-way ANOVA (interaction: F(3,44) = 29.9, ***p < 0.0001 followed by Bartlett’s test). Sidak’s multiple comparisons test: *p < 0.05 vs. Sham, #p < 0.05 vs. vector control. (B) In the corner test, normal mice make equal left and right turns so the ratio of turns is close to 1.0. After a stroke, animals revealed a sensorimotor deficit of biased turn behavior due to the side of ischemic damage in the sensorimotor cortex. ND1 treatment showed a significant correction in this sensorimotor functional deficit. N = 6/group, two-way ANOVA (interaction: F(2,15) = 19.91, ***p < 0.001 followed by Bartlett’s test). Sidak’s multiple comparisons test: *p < 0.05 vs. Sham, #p < 0.05 vs. vector control. (C) Long-term psychological behaviors were tested 4 months after stroke. In the sucrose preference test, sham animals showed a marked increase in consuming the sucrose solution compared to saline, while stroke resulted in a significantly reduced interest in the sucrose solution. Stroke mice that received ND1 treatment maintained a similar interest in drinking the sucrose solution as sham mice. N = 12–14/group, one-way ANOVA (F(2,36) 3.447, p = 0.0427), *p < 0.05 vs. Sham. (D) In the forced swim test, stroke mice exhibited significantly longer idle time in the water, indicative of a chronically developed post-stroke depression-like phenotype. This depression-like behavior was significantly corrected in stroke mice treated with ND1. N = 6/group, One-way ANOVA (F(4,82) = 13.27, ****p < 0.0001) followed by Holm–Sidak’s multiple comparisons test: *p < 0.05 vs. before stroke, #p < 0.05 vs. stroke control. (E) Tail suspension test of depression-like behavior in rodents. Stroke mice were observed to spend a longer time immobile compared to sham controls. ND1 treatment yielded a trend of reducing the immobility time. N = 14/group, one-way ANOVA (interaction: F(2,39) = 2.53, ***p = 0.0926 followed by Bartlett’s test).