Fig. 3. MiR-195 expression is reduced in hippocampal brain tissue and cultured primary neurons of ApoE4 mice; modulating miR-195 levels regulates synaptojanin 1 expression.

a Levels of miR-195 were reduced in 12-month old ApoE4 hippocampal brain tissue (log₂FC: −0.283 ± 0.069) when compared to those in ApoE3 mice (log₂FC: −0.036 ± 0.034). N = 11–13/group with both males and females; **p = 0.0096 with ANOVA tests. A nominal reduction in miR-195 levels was seen in ApoE^−/− brains with no statistical significance (log₂FC: −0.125 ± 0.067, p = 0.48). b Levels of miR-195 in ApoE^−/− neurons treated with ApoE4-CM were reduced (log₂FC = −0.314 ± 0.073,) when compared to levels of those treated with ApoE3-CM (log₂FC: 0.184 ± 0.094). N = 5/group; **p = 0.003 with independent-samples t-tests. c Differences in miR-195 expression levels between ApoE3-CM and ApoE4-CM treated neurons were abolished in the presence of RAP. The treatment of RAP in the presence of ApoE3-CM led to a reduction in miR-195 levels (log₂FC: −1.648 ± 0.125; p < 0.0001), whereas in ApoE4-CM treated conditions, miR-195 levels were much lower at baseline with a trend of improvement in the presence of RAP treatment (ApoE4 CM + BSA log₂FC: −3.193 ± 0.144 versus ApoE4 CM + RAP log₂FC: −2.678 ± 0.054; p = 0.052). N = 3/group; ****p < 0.0001 by One-Way ANOVA tests. d Synj1 protein levels were reduced with miR-195 over-expression but not miR-374 over-expression in ApoE^−/− hippocampal neurons in the presence of ApoE4-CM. N = 4/group; synj1 levels with miR-195: 62.87 ± 4.48% of controls, **p = 0.001; with miR-374: 102.4 ± 7.77% of controls, p = 0.93.