Age- and sex-dependent effects on numbers of neuropeptide Y-immunopositive hilar GABAergic interneurons in apoE-KI mice.

<p><b><i>A, B</i></b>, Histograms showing the total number of hilar GABAergic interneurons immunopositive for neuropeptide Y in female (<b><i>A</i></b>) or male (<b><i>B</i></b>) apoE-KI mice at the identified ages. Female and male apoE-KI mice show that NPY-positive interneuron levels are similarly apoE genotype-independent, but are age-dependent in opposite directions, whereby NPY-positive interneurons decrease and increase with age in females and males, respectively. There was no interaction between the two variables (by 2-way ANOVA) for either sex. <b><i>C, D</i></b> Quantification of NPY-positive hilar interneurons in female and male apoE3-KI (<b><i>C</i></b>) and apoE4-KI (<b><i>D</i></b>) mice at 1, 3, 6, 12, and 16 months of age (n = 6−12 mice per group). Both genotypes show age-independent, but sex-dependent, effects on NPY-positive interneurons by 2-way ANOVA. *<i>p</i><0.05; **<i>p</i><0.01; ***<i>p</i><0.001 in male apoE-KI mice compared to female apoE-KI mice at the same age (<i>post-hoc</i> Bonferroni test). <b><i>E–H</i></b>, Representative images (200x) of neuropeptide Y–immunostained sections of the hilus of female apoE3-KI (<b><i>E</i></b>), female apoE4-KI (<b><i>F</i></b>), male apoE3-KI (<b><i>G</i></b>), and male apoE4-KI (<b><i>H</i></b>) mice at 16 months of age.