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Fig. 4 | Molecular Brain

Fig. 4

From: Forebrain-specific conditional calcineurin deficiency induces dentate gyrus immaturity and hyper-dopaminergic signaling in mice

Fig. 4

Rescue of immature dentate gyrus phenotype and impaired nest building behavior by chronic rolipram treatment in Cn mutant mice. a Immunostaining images of calbindin (upper panels) and phospho-CREB (lower panels). Scale bars, 200 μm. G, granule cell layer; h, hilus. b–g Bar graphs showing the number of calbindin-positive cells (b; Bartlett test: genotype, P = 0.0037, drug, P = 0.11; Friedman test: genotype effect: F(1, 11) = 33.52, P < 0.0001; drug effect: F(1, 11) = 13.84, P = 0.0034; interaction: F(1, 11) = 9.79, P = 0.0096), the number of phospho-CREB-positive cells (c; Bartlett test: genotype, P = 0.016, drug, P = 0.024; Friedman test: genotype effect: F(1, 16) = 45.15, P < 0.0001; drug effect: F(1, 16) = 7.37, P = 0.015; interaction: F(1, 16) = 3.59, P = 0.076), the number of doublecortin (Dcx)-positive cells (d; genotype effect: F(1,10) = 6.50, P = 0.029; drug effect: F(1, 10) = 2.04, P = 0.18; interaction: F(1, 10) = 4.22, P = 0.067), number of calretinin (CR)-positive cells (e; Bartlett test: genotype, P = 0.023, drug, P = 0.13; Friedman test: genotype effect: F(1, 10) = 10.81, P = 0.0082; drug effect: F(1, 10) = 6.15, P = 0.033; interaction: F(1, 10) = 5.22, P = 0.046), GFAP immunoreactivity (f; Bartlett test: genotype, P = 0.016, drug, P = 0.024; Friedman test: genotype effect: F(1, 11) = 33.52, P = 0.00012; drug effect: F(1, 11) = 12.14, P = 0.0051; interaction: F(1, 11) = 10.23, P = 0.0085), and nest-building score (g; genotype effect: F(1,55) = 17.70, P < 0.0001; drug effect: F(1, 55) = 4.45, P = 0.040; interaction: F(1, 55) = 3.82, P = 0.056). *P < 0.05, **P < 0.01, two-way ANOVA or Friedman test followed by multiple comparison test. Bar graphs show means ± SEM. Each dot represents one mouse. h–o Expression levels of P-Ser845 GluA1 (h, l), P-Thr202/Tyr204 ERK2 (i, m), P-Thr34 DARPP-32 (j, n), and P-Ser133 PDE4B1 (k, o) in the DG slices from vehicle (Veh)-treated mice (h–k) or rolipram (Rol)-treated mice (l–o) with or without preincubation with SKF81297. The data were normalized to total protein and values obtained with untreated slices from vehicle-treated control mice. The expression levels of total proteins were not altered significantly between genotypes or in response to SKF81297. The original blots are included in Additional file 1: Fig. S7. *P < 0.05, **P < 0.01, two-way ANOVA or Friedman test. h Bartlett test: genotype, P = 0.00075, SKF81297, P = 0.013; Friedman test: Genotype effect: F(1, 42) = 15.55, P = 0.00030; effect of SKF81297: F(2, 42) = 26.14, P < 0.0001; interaction: F(2, 42) = 0.45, P = 0.64. i Genotype effect: F(1, 42) = 23.11, P < 0.0001; effect of SKF81297: F(2, 42) = 18.57, P < 0.0001; interaction: F(2, 42) = 0.26, P = 0.77. j Genotype effect: F(1, 42) = 18.35, P = 0.0001; effect of SKF81297: F(2, 42) = 12.94, P < 0.0001; interaction: F(2, 42) = 0.78, P = 0.46. k Genotype effect: F(1, 36) = 42.55, P < 0.0001; effect of SKF81297: F(2, 36) = 4.07, P = 0.026; interaction F(2, 36) = 1.87, P = 0.17. l Genotype effect: F(1, 42) = 0.015, P = 0.90; effect of SKF81297: F(2, 42) = 15.41, P < 0.0001; interaction: F(2, 42) = 0.13, P = 0.88. m Genotype effect: F(1, 42) = 0.14, P = 0.71; effect of SKF81297: F(2, 42) = 19.15, P < 0.0001; interaction: F(2, 42) = 0.068, P = 0.93. n Genotype effect: F(1, 42) = 5.09, P = 0.0293; effect of SKF81297 F(2, 42) = 12.52, P < 0.0001; interaction: F(2, 42) = 0.39, P = 0.68. o Genotype effect: F(1, 36) = 36.62, P < 0.0001; effect of SKF81297: F(2, 36) = 7.04, P = 0.0026; interaction: F(2, 36) = 1.34, P = 0.27. Data are shown as means ± SEM

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