Fig. 6: Maternal behavior protects against stress vulnerability via upregulating mPFC IGF-1 levels in adolescent mice.

a Graphic representation of maternal behavior in mice; Measurement of maternal behavior sample points in WT mice exposed to maternal separation for 0, 10 min × 2, and 180 min × 1. Data are presented the mean ± SEM (n = 11 mice for no maternal separation group, n = 8 mice for maternal separation on 10 min × 2 group, n = 8 mice for maternal separation on 180 min × 1 group; one-way ANOVA and Bonferroni’s multiple comparison test). b Correlation analysis between social interaction ratio and maternal behavior sample points in WT mice experiencing maternal separation. The white, red, and blue dots represent 0, 10 min × 2, and 180 min × 1 groups, respectively. The Spearman correlation coefficient r² and two-sided p value are shown (n = 8 mice for no maternal separation group, n = 8 mice for 10 min × 2 group, n = 10 mice for 180 min × 1 group). Correlation analysis between mPFC IGF-1 levels and maternal behavior sample points (c), or social interaction ratio (d) in WT mice experiencing maternal separation. The white, red, and blue dots represent 0, 10 min × 2, and 180 min × 1 groups, respectively. The Spearman correlation coefficient r² and two-sided p value are shown (n = 6 mice for each group). e Graphic representation of L and LnL treatment; Schematic representation of the experimental procedure for maternal separation on 180 min × 1 or not, and AcSD paradigm and behavioral tests with L or LnL dams. f Measurement of maternal behavior sample points in WT mice exposed to maternal separation for 180 min × 1 or 0, with L or LnL dams. Data are presented the mean ± SEM (n = 6 mice for 180 × 1 + L group, n = 6 mice for 180 × 1 + LnL group, n = 6 mice for 0 + L group; n = 7 mice for 0 + LnL group; one-way ANOVA and Bonferroni’s multiple comparison test). g Measurement of IGF-1 levels in the mPFC, in the hippocampus, and in the blood in WT mice exposed to maternal separation for 180 min × 1 or 0, with L or LnL dams. Data are presented the mean ± SEM (n = 5 for each group; one-way ANOVA and Bonferroni’s multiple comparison test). h Representative immunoblots of LAP/LIP ratio and DRP1 expressions in the mPFC neurons of WT mice exposed to maternal separation for 180 min × 1 or 0, with L or LnL dams. Data are representative of three independent experiments. i, j Behavioral tests of WT mice exposed to maternal separation for 180 min × 1 or 0, with L or LnL dams. Measurement of social interaction ratio (i), and the percentage of sucrose preference (j) in WT mice with indicative treatments. Data in (i, j) are presented as the mean ± SEM (n = 13 mice for 180 × 1 groups, n = 15 mice for 0 groups; one-way ANOVA and Bonferroni’s multiple comparison test). k Schematic representation of the experimental procedure for maternal separation on 10 min × 2 or not, and AcSD paradigm and behavioral tests with saline- or CNO-treated dams. l The location of the cannula tips in Esr-2A-Cre female mice; Fluorescence microscopy image of representative field showed mCherry expression in the MPOA injected with AAV-DIO-hM4Di-mCherry. Scale bar: 100 μm. n = 4 dams for each group. m Measurement of maternal behavior sample points in WT mice exposed to maternal separation for 10 min × 2 or 0, with saline- or CNO-treated dams. Data are presented the mean ± SEM (n = 6 mice for 0 + Saline group, n = 6 mice for 10 × 2 + Saline group, n = 5 mice for 0 + CNO group; n = 6 mice for 10 × 2 + CNO group; one-way ANOVA and Bonferroni’s multiple comparison test). n Measurement of IGF-1 levels in the mPFC, in the hippocampus and in the blood in WT mice exposed to maternal separation for 10 min × 2 or 0, with saline- or CNO-treated dams. Data are presented the mean ± SEM (n = 5 for each group; one-way ANOVA and Bonferroni’s multiple comparison test). o Representative immunoblots of LAP/LIP ratio and DRP1 expressions in mPFC neurons of WT mice exposed to maternal separation for 10 min × 2 or 0, with saline- or CNO-treated dams. Data are representative of three independent experiments. p, q Behavioral tests of WT mice exposed to maternal separation for 10 min × 2 or 0, with saline- or CNO-treated dams. Measurement of social interaction ratio (p), and the percentage of sucrose preference (q) in WT mice with indicative treatments. Data in (p, q) are presented as the mean ± SEM (n = 14 mice for 0 + Saline group, n = 14 mice for 10 × 2 + Saline group, n = 13 mice for 0 + CNO group; n = 14 mice for 10 × 2 + CNO group; one-way ANOVA and Bonferroni’s multiple comparison test). r. Schematic representation of molecular pathway that various maternal behavior levels mediate stress susceptibility via the “two-hit” hypothesis. See also Supplementary Figs. 11–16. Source data are provided as a Source Data file.