Fig. 8: Microglia-behavior relationships in aging mice.

a IBA1-positive microglia in the ventral tegmental area (VTA) and nucleus accumbens (NAc) of young-adult (4 months) and late-middle-aged (18 months) mice. b Boxplots of VTA and NAc microglia densities in young-adult (black; n = 28 mice) and late-middle-aged (gray; n = 29 mice) mice (n-way ANOVA; post-hoc Tukey-Kramer; two-sided; Age: p = 0; Region: p = 0; VTA post-hoc: p = 0.004). c Relationship between VTA and NAc microglia densities and performance on foraging task (robust regression; two-sided; Young VTA: p = 0.12; p = 0.004; Young NAc: p = 0.13; Middle-aged NAc: p = 0.038). d PCA plot of select microglia-enriched proteins from the membrane fraction (left). Average protein intensities of microglia-enriched proteins separated by age and cognitive status (middle; n-Way ANOVA; two-sided; p = 0.014; n = 6 young-adult, n = 5 middle-aged-unimpaired, n = 7 middle-aged-impaired mice). Heat plot of microglia-enriched protein abundances and bar plots of their relationship with cognitive status and age (*p < 0.05; linear probability model). e Heat plot of ECM proteoglycan abundances from the membrane fraction and bar plots of their relationship with total microglia-enriched protein and synapse receptor abundances (*p < 0.05; linear probability model). f Correlation network plots of relationships between cognition and ECM, synapse, and microglia abundances from both behavioral experiments in this study shown separately for young-aged and middle-aged mice. Numbers are r values and the width of connections between variables scales with the strength of their correlation (linear regression). In all boxplots, boxes represent interquartile ranges (IQR; 25–75 percentiles), middle lines represent medians, and whiskers extend +/− 1.5*IQR. Source data are provided in the file Source Data - Fig. 8 and all statistics are provided in Supplementary Data 6. * represents p < 0.05, ** represents p < 0.01, *** represents p < 0.001.