Fig. 3: p11 and SMARCA3 in PV neurons mediate the response to chronic SSRIs. | Molecular Psychiatry

Fig. 3: p11 and SMARCA3 in PV neurons mediate the response to chronic SSRIs.

From: Activation of the p11/SMARCA3/Neurensin-2 pathway in parvalbumin interneurons mediates the response to chronic antidepressants

Fig. 3

a, b Representative western blots (a) and bar graph summary (b) of p11 and β-actin levels in the hippocampus of WT mice, or in mice with conditional deletion of p11 in PV cells (p11-cKO PV) or in CCK cells (p11-cKO CCK). Mice were injected with saline (veh) or citalopram (cit) once a day for 14 days. Two-way ANOVA, interaction, F (2, 18) = 34.19. ****p < 0.0001. ####p < 0.0001 vs. WT treated with veh, n.s not significant. c Representative immunohistochemical images showing localization of Neurensin-2 protein in PV positive cells located in the DG of WT mouse. Arrowheads and box highlight immunopositive cells in the SGZ. Scale bar, 50 μm. d Western blot scan (top) and quantification (bottom) of hippocampal Neurensin-2 protein expression in WT mice and in mice with SMARCA3 deletion in PV cells (SMARCA3 cKO). Unpaired t test, **p = 0.007, n = 5/group. e Western blot scan (top) and quantification (bottom) of hippocampal Neurensin-2 protein expression in WT mice and in mice with SMARCA3 deletion in PV cells after chronic treatment with fluoxetine (flx). Dashed line indicates Neurensin-2 levels in mice treated with vehicle (100%). Unpaired t test, ***p = 0.0003, n = 4/group. f–h Behavioral tests in WT or in mice with deletion of SMARCA3 in PV cells (SMARCA3-cKO) after 21 days of treatment with vehicle (veh) or fluoxetine (flx). f Forced swim test (FST). Two-way ANOVA; interaction, F (1, 129) = 12.08, P = 0.0007; genotype, F = 0.97, P = 0.32; treatment, F = 0.5, P = 0.82. *p = 0.038 for WT mice, *p = 0.046 for cKO mice, **p = 0.007, n = 32, 39, 30, 32. g Tail suspension test (TST). Two-way ANOVA; F (1, 62) = 33.35, interaction, P < 0.0001; genotype, F = 4.19, P = 0.044; treatment, F = 8.37, P = 0.005. *p = 0.035, ****p < 0.0001, n = 18, 17, 20, 11. h Novelty suppressed feeding (NSF). Two-way ANOVA; interaction, F (1, 129) = 7.17, P = 0.008; genotype, F = 15.93, P = 0.0001; treatment, F = 14.16, P = 0.0003. ****p < 0.0001, n = 32, 39, 30, 32. Molecular weights are indicated in KDa.

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