Fig. 6

The treatment with MLN-4924 of mice fed with the HFD ameliorates synaptic IR and memory impairment. a, b Representative immunoblots and quantification of total hippocampal extracts showing a reduction in pIRS1/IRS1 ratio upon the MLN-4924 treatment of wild-type or heterozygous TBA2.1 fed with HFD. IRS1 protein level was normalized to β-actin. n = 5. *P < 0.05 versus control, by two-way ANOVA followed by Tukey´s post-hoc test. c, d Quantification of fEPSP slope values in wild-type and heterozygous TBA2.1 mice fed with HFD and injected with MLN-4924 or vehicle shows the rescue of LTD upon the treatment with MLN-4924. e Averaged fEPSP slope values measured 180–210 min after LTD induction. n = 12 for groups 1 and 3; n = 10 for group 2; n = 11 for group 4. f, g Behavioral assessment in mice injected with MLN-4924 or vehicle. f Scatter dot plot shows a rescue of the discrimination index of the new located (NLR) without alterations in replaced object location (NOR, g). In f n = 10 for group; n = 8 for groups 2 and 3; n = 11 in group 4. In g n = 8 for group 1; n = 6 for group 2; n = 7 for group 3; n = 9 for group 4. n indicates the number of animals. ***P < 0.001, *P < 0.05 versus control, by two-way ANOVA followed by Bonferroni’s post-hoc test. n.s. = non-significant. Data are presented as the mean ± SEM