Fig. 1

IDE absence has specific effects on hippocampal microglia, triggering microglia phenotypic modulation without affecting astrocytes. A Representative confocal images of immunohistochemistry experiments on 12-month-old WT and IDE-KO mice. Iba1 and GFAP are used as microglial and astroglial markers, respectively. Nuclei are stained with DAPI. Insets show close-ups where morphological changes in IDE-KO microglia can be appreciated. The intensity of labeling in WT inset has been multiplied by a factor of 4, to help visualization. B Total hippocampal volume (t-test; p = 0.29). C Astrogliosis, measured as the percentage of area occupied by GFAP labeling (t-test; p = 0.57). D Microgliosis, measured as the percentage of area occupied by Iba1 labeling (U Mann–Whitney test; p = 0.04). In B–D each point represents an individual mouse (squares = males, circles = females). Horizontal lines depict the mean ± SEM. N = 4–6 mice per genotype and sex. Statistical differences were initially assessed by two-way ANOVA considering the factors genotype and sex. Since no sex-differences were detected (hippocampal volume p = 0.383, Iba1⁺ area p = 0.573, GFAP⁺ area p = 0.405), male and female mice of the same genotype were pooled. *p < 0.05. E, F Object location test (OLT) and Novel Object Recognition Test (NORT) results. N = 10 mice per genotype and sex. Each point represents an individual mouse. Lines depict the median ± interquartile range. Statistical differences in OLT and NORT were assessed by two-way ANOVA, considering the factors genotype and sex, followed by all pairwise multiple comparisons using the Holm–Sidak method. Only biologically relevant differences are shown. **p < 0.01