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

<p><b><i>A, B</i></b>, Histograms showing the total number of somatostatin-positive hilar GABAergic interneurons in female (<b><i>A</i></b>) or male (<b><i>B</i></b>) apoE3-KI or apoE4-KI mice at 1, 3, 6, 12, and 16 months of age (n = 6−12 mice per group). Female apoE-KI mice show an apoE isoform-dependent and age-dependent effect, but no interaction between the two variables by 2-way ANOVA <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0053569#pone.0053569-AndrewsZwilling1" target="_blank">[28]</a>. Male apoE-KI mice demonstrate an age-dependent effect, but no apoE isoform–dependent effects. No interaction was detected between the two variables. *<i>p</i><0.05; ***<i>p</i><0.005 in female apoE4-KI mice compared to female apoE3-KI mice at the same age (<i>post-hoc</i> Bonferroni test). <b><i>C, D</i></b>, Quantification of somatostatin-positive hilar GABAergic interneurons in female and male apoE3-KI (<b><i>C</i></b>) or apoE4-KI (<b><i>D</i></b>) mice at 1, 3, 6, 12, and 16 months of age (n = 6−12 mice per group). ApoE3-KI mice have age-dependent and sex-independent effects, whereas apoE4-KI mice show an age-independent and sex-dependent effect. Both apoE genotypes show an interaction between age and sex by 2-way ANOVA. *<i>p</i><0.05; ***<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 somatostatin-immunostained hilar sections 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. <b><i>I, J</i></b>, Escape latency in hidden platform days 1−5 correlated inversely with the number of somatostatin-positive hilar interneurons in female apoE4-KI mice (<i>I</i>, n = 12) but not female apoE3-KI mice (<b><i>J</i></b>, n = 10) at 16 months of age <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0053569#pone.0053569-AndrewsZwilling1" target="_blank">[28]</a>.