Fig. 6: Optogenetic rescue of young mouse depression model via the FGFR1–Notch–BDNF axis in the dentate gyrus.
From: Dysregulation of FGFR1 signaling in the hippocampus facilitates depressive disorder
a A schematic representation and timeline showing the viral injection in Fgfr1flox/flox mice and administration of corticosterone with blue light. b Anxiety index, total immobility and sucrose preference in Fgfr1flox/flox mice. The experimental groups included: FGFR1-cKO mice with V3W, in which a Cre virus was injected into the hippocampal dentate gyrus of Fgfr1flox/flox mice (V3W); FGFR1-cKO mice, in which an optoFGFR1 virus was injected into the hippocampal dentate gyrus of Fgfr1flox/flox mice with C1W under dark room condition (dark); FGFR1-cKO mice, in which an optoFGFR1 virus was injected into the hippocampal dentate gyrus of Fgfr1flox/flox mice with C1W and blue LED stimulation for 7 days (light); FGFR1–EGFP mice, in which a EGFP-virus (control virus) was injected into the hippocampal dentate gyrus of Fgfr1flox/flox mice followed by C1W and blue LED stimulation for 7 days (EGFP light). The data are presented as means ± s.e.m.; n = 5 (FGFR1-cKO;V3W), n = 5 (FGFR1-cKO; dark), n = 5 (FGFR1-cKO; light), n = 4 (FGFR1–EGFP; EGFP light) Fgfr1flox/flox mice were included for each condition. For anxiety index, a one-way ANOVA revealed no significant effect on anxiety index (F(3,15) = 1.11, P = 0.3758). Post hoc comparisons using Tukey’s multiple comparisons test showed no significant differences between any groups (all P > 0.05). For total immobility, one-way ANOVA revealed a significant main effect on immobility time in the tail suspension test (F(3,20) = 21.77, P < 0.0001). Post hoc comparisons using Tukey’s multiple comparisons test showed that immobility time was significantly increased in dark compared with V3W (P < 0.0001) and light significantly reduced immobility compared with dark (P < 0.0001). EGFP light also significantly increased immobility compared with light (P = 0.0025), while no significant difference was found between dark and EGFP light (P = 0.8268) or between V3W and light (P = 0.7943). For sucrose preference, a one-way ANOVA revealed a significant main effect of sucrose preference (F(3,15) = 23.43, P < 0.0001). Post hoc comparisons using Tukey’s multiple comparisons test showed that the V3W exhibited significantly higher preference compared with the dark (P < 0.0001) and EGFP light (P < 0.0001). Dark showed significantly lower preference compared with light (P = 0.0025), while no significant difference was observed between the dark and EGFP light (P = 0.4867) or between the V3W and light (P = 0.4264). ns, not significant; ***P < 0.001; ****P < 0.0001. c Anxiety index, total immobility and sucrose preference in old Fgfr1flox/flox mice. The experimental groups included: old FGFR1-cKO mice, in which an optoFGFR1 virus was injected into the hippocampal dentate gyrus of Fgfr1flox/flox mice with C1W under dark room condition (dark); old FGFR1-cKO mice, in which an optoFGFR1 virus was injected into the hippocampal dentate gyrus of Fgfr1flox/flox mice with C1W and blue LED stimulation for 7 days (light); old FGFR1–EGFP mice, in which a EGFP-virus (control virus) was injected into the hippocampal dentate gyrus of Fgfr1flox/flox mice followed by C1W and blue LED stimulation for 7 days (EGFP light). The data are presented as means ± s.e.m.; n = 9 (dark); n = 11 (light); and n = 10 (EGFP Light) old Fgfr1flox/flox mice were included for each condition. For the Old-FGFR1 anxiety index, a one-way ANOVA revealed no significant main on anxiety index (F(2,27) = 0.4555, P = 0.6389). Post hoc comparisons using Tukey’s multiple comparisons test showed no significant differences between the dark and light (P = 0.9526), Dark and EGFP light (P = 0.8187) or light and EGFP light (P = 0.6193). For the Old-FGFR1 total immobility, one-way ANOVA revealed no significant main effect on immobility time (F(2,29) = 0.01364, P = 0.9865). Post hoc comparisons using Tukey’s multiple comparisons test showed no significant differences between the dark and light (P = 0.9926), dark and EGFP light (P = 0.9858) or light and EGFP light (P = 0.9988). For the Old-FGFR1 sucrose preference, one-way ANOVA revealed no significant main on preference (F(2,27) = 0.0674, P = 0.935). Post hoc comparisons using Tukey’s multiple comparisons test showed no significant differences between the dark and light (P = 0.9966), dark and EGFP light (P = 0.9634) or light and EGFP light (P = 0.9349). ns, not significant. d A schematic representation and timeline showing the administration of vehicle and corticosterone in WT old mice. e FGFR1 qRT–PCR results in vehicle- or corticosterone- administrated mice after behavior tests. The data are represented as means ± s.e.m.; n = 10 for old V3W, n = 5 for old C1W and n = 9 for old C3W mice. A one-way ANOVA revealed a significant main effect of corticosterone treatment (F(2,21) = 17.44, P < 0.0001). Post hoc comparisons using Tukey’s multiple comparisons test showed that the both the C1W group (P = 0.003) and the C3W group (P < 0.0001) had significantly higher FGFR1 mRNA levels compared with V3W. No significant difference was observed between the C1W and C3W groups (P = 0.6152). **P < 0.01; ****P < 0.001. f Western blot image and quantification for FGFR1 and GAPDH in vehicle- or corticosterone-administrated mice after behavior tests. The data are represented as means ± s.e.m.; n = 12 old WT mice were included for each condition. An unpaired two-tailed t-test revealed a significant difference between the V3W and C3W groups (t(22) = 5.718, P < 0.0001). ****P < 0.0001.
