Fig. 8: Microglial-derived IGF-1 inhibits neuronal C/EBPβ-DRP1 axis to prevent stress susceptibility in adolescent mice.

a Schematic representation of the experimental procedure of virus injection, and AcSD paradigm and behavioral tests for Cx3cr1-Cre mice with LnL dams. b The location of the cannula tips and fluorescence microscopy image of representative field showed mCherry expression in the mPFC injected with AAV-hSyn-mCherry; Fluorescence microscopy image of representative field showed GFP expression and Iba1 (Purple) in the mPFC injected with AAV-MG1.2-DIO-GFP in Cx3cr1-Cre mice. Scale bar: 100 μm (left), 50 μm (right). n = 3 mice for each group. c, d Representative immunoblots and quantification of LAP/LIP ratio, and IGF-1 and DRP1 expressions in Cx3cr1-Cre mice exposed to AcSD paradigm and virus injection of AAV-MG1.2-DIO-shControl or -shIGF-1 and AAV-hSyn-mCherry or -LIP, with LnL dams. Data are representative of three independent experiments. Data are presented the mean ± SEM (n = 4 for each group; one-way ANOVA and Bonferroni’s multiple comparison test). e Measurement of maternal behavior sample points in Cx3cr1-Cre mice with indicative treatments. Data are presented the mean ± SEM (n = 5 mice for each group; one-way ANOVA and Bonferroni’s multiple comparison test). f Measurement of Dnm1l mRNA levels in the mPFC neurons of Cx3cr1-Cre mice with indicative treatments. Data are presented the mean ± SEM (n = 6 for each group; one-way ANOVA and Bonferroni’s multiple comparison test). g Measurement of mitochondrial MMP and ATP levels in the mPFC of Cx3cr1-Cre mice with indicative treatments. Data are presented the mean ± SEM (n = 8 for each group; one-way ANOVA and Bonferroni’s multiple comparison test). h, i Behavioral tests of Cx3cr1-Cre mice exposed to AcSD paradigm and virus injection of AAV-MG1.2-DIO-shControl or -shIGF-1 and AAV-hSyn-mCherry or -LIP, with LnL dams. Measurement of social interaction ratio (h), and the percentage of sucrose preference (i) in Cx3cr1-Cre mice with indicative treatments. Data in (h, i) are presented as the mean ± SEM (n = 12 mice for each group; one-way ANOVA and Bonferroni’s multiple comparison test). j Schematic representation of the experimental procedure of virus injection, and AcSD paradigm and behavioral tests for Cx3cr1-Cre mice with CNO-treated dams. k The location of the cannula tips and fluorescence microscopy image of representative field showed mCherry expression in the mPFC injected with AAV-hSyn-mCherry; Fluorescence microscopy image of representative field showed GFP expression and Iba1 (Purple) in the mPFC injected with AAV-MG1.2-DIO-GFP in Cx3cr1-Cre mice. Scale bar: 100 μm (left), 50 μm (right). n = 3 mice for each group. l, m Representative immunoblots and quantification of LAP/LIP ratio, and IGF-1 and DRP1 expressions in Cx3cr1-Cre mice exposed to AcSD paradigm and virus injection of AAV-MG1.2-DIO-GFP or -IGF-1 and AAV-hSyn-mCherry or -LAP, with CNO-treated dams. Data are representative of three independent experiments. Data are presented the mean ± SEM (n = 4 for each group; one-way ANOVA and Bonferroni’s multiple comparison test). n Measurement of maternal behavior sample points in Cx3cr1-Cre mice with indicative treatments. Data are presented the mean ± SEM (n = 4 mice for each group; one-way ANOVA and Bonferroni’s multiple comparison test). o Measurement of Dnm1l mRNA levels in the mPFC neurons of Cx3cr1-Cre mice with indicative treatments. Data are presented the mean ± SEM (n = 5 for each group; one-way ANOVA and Bonferroni’s multiple comparison test). p Measurement of mitochondrial MMP and ATP levels in the mPFC of Cx3cr1-Cre mice with indicative treatments. Data are presented the mean ± SEM (n  = 6 for each group; one-way ANOVA and Bonferroni’s multiple comparison test). q, r Behavioral tests of Cx3cr1-Cre mice exposed to AcSD paradigm and virus injection of AAV-MG1.2-DIO-GFP or -IGF-1 and AAV-hSyn-mCherry or -LAP, with CNO-treated dams. Measurement of social interaction ratio (q), and the percentage of sucrose preference (r) in Cx3cr1-Cre mice with indicative treatments. Data in (q, r) are presented as the mean ± SEM (n = 10 mice for GFP + mCherry group; n = 9 mice for IGF-1 + mCherry group; n = 9 mice for IGF-1 + LAP group; one-way ANOVA and Bonferroni’s multiple comparison test). See also Supplementary Fig. 19. Source data are provided as a Source Data file.