Fig. 3: The role of REST in the depressive phenotype and sertraline-induced gene transcription in vivo.
From: Transcription factors Lef1 and Rest stimulate recovery from depressive states
a, b Validation of shRNA targeting endogenous REST. Immunostained images of cultured cortical neurons. Scale bar, 50 μm. Welch’s t-test; shRNA positive, 140; others, 13,327 cells. c–f Effects of REST knockdown in vivo. c The experimental scheme (top) and the brain sections demonstrating the shRNA-expressing populations (bottom and right). The dotted area denotes the PFC; PrL, prelimbic; IL, infralimbic. Scale bar, 1000 and 500 μm, respectively. Changes in SI-rates in shRNA expressing mice. SI-rates before (d) and after social defeat (e), and SI-rates after chronic stress, normalized to the pre-stress values (f). Mean ± sem. Welch’s t-test and two-way ANOVA; shScramble, 16; shREST, 16 mice. Effects of sertraline in vivo. g The experimental schedule. Effect of sertraline on REST-activity in the anterior region of the cortex (h) and SI-rates (i) without social defeat stress. Welch’s t-test for (h) and (i). Number of mice: 6, 6 (h); 10, 10 (i). j Experimental schedule (top) and changes in SI-rates (bottom). Data include those shown in Fig. 1. SI-rates were normalized to the control group for each day. Mean ± sem; two-way ANOVA for defeat and defeat + sertraline. Number of mice for control, defeat, and defeat + sertraline — day 1: 90, 126, 21; day 3: 90, 126, 21; day 8: 27, 38, 15; day 15: 24, 33, 15. k Distribution of log2-fold changes in REST downstream gene expression; red, control versus defeat; blue, control versus defeat with sertraline treatment. F-test, 994 genes.
