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. Author manuscript; available in PMC: 2019 Oct 13.
Published in final edited form as: Mol Psychiatry. 2019 Apr 12;25(5):951–964. doi: 10.1038/s41380-019-0421-5

Figure 1. miR-218 downregulation in the mPFC induces depression-like behaviors in mice.

Figure 1.

(a) Schematic illustration of the miR-218 antagomiR (Ant-miR-218). AntagomiRs induce degradation of specific microRNAs in vivo upon binding them with high specificity. (b) Timeline of experiments. (c) Degradation of miR-218 in the mPFC leads to social avoidance following a single session of social defeat (SSD). Time in the interaction zone: Three-way ANOVA: main effect of stress: F(1,58)= 12.40; p=0.001; main effect of target: F(1,58)= 5.022; p=0.029; and main effect of antagomiR: F(1,58)= 10.24; p= 0.002. Significant effect of stress by target by antagomiR interaction: F(1,58)= 4.87; p=0.031. Post hoc Tukey test reveals reduced time in the social interaction zone in SSD-Ant-miR-218 (n=9) during the session with target present as compared to SSD-Ant-scrambled (n=8), and Control-Ant-scrambled (n= 8), *p<0.05; and as compared to Control-Ant-miR-218 (n= 8); †p<0.01. Importantly, Control-Ant-scrambled and Control-Ant-miR-218 groups spend significantly more time exploring the social interaction zone during the session with target present in comparison to target absent; ¤p<0.001. (d) Social interaction ratio: Two-way ANOVA: main effect of stress: F(1,29)=16.39; p=0.0004; and significant stress by antagomiR interaction: F(1,29)=6.03; p=0.02. Post hoc Tukey test shows reduced social interaction ratio in SSD-Ant-miR-218 in comparison to SSD-Ant-scrambled, *p<0.05; and to Control-Ant-scrambled, and Control-Ant-miR-218, †p<0.01. (e) Downregulation of miR-218 in the mPFC of adult mice increases percentage of immobility time in the forced swimming test (FST): t(23)=2.52; *p= 0.019, different from Ant-scrambled. (f) Timeline of CSDS experiment and intranasal infusion of Ant-Scrambled (n=7) or Ant-miR-218 (n=6) in resilient mice. (g) Time in the social interaction (SI) zone with Target present before and after intranasal infusion: Two-way ANOVA: main effect of session: F(1,22)= 6.098; p= 0.021; main effect of infusion: F(1,22)= 3.61; p= 0.07, and significant session by treatment interaction: F(1,22)= 5.84; p= 0.024). Post hoc Tukey test shows reduced time in the social interaction zone with the target present in Ant-miR-218 in comparison to Ant-scrambled during SIT 2, *p<0.05; and to Ant-scrambled, and Ant-miR-218 during SIT 1, †p<0.05. (h) Timeline of intranasal infusion of Ant-Scrambled or Ant-miR-218 in wild-type mice. (i) Intranasal infusion of Ant-miR-218 increases percentage of immobility time in the FST: t(14)=2.17; p=0.04. (j) Time in center: t(14)=0.621; p=0.54. (k) Distance moved: t(14)=0.55; p=0.59.