Fig. 5.

Transgenic over-expression of heat-shock factor 1 (HSF1) ameliorates Alzheimer’s disease-like cognitive deficits in human amyloid precursor protein (PDAPP) mice. (a) Time exploring a novel object was significantly increased in PDAPP/HSF1 mice, indicating improved memory of a previously encountered object (p as indicated, Welch’s correction on Student’s t-test). (b) Although performance in the Morris water maze in PDAPP and PDAPP/HSF1 groups was significantly impaired with respect to that of non-transgenic (NTg) littermates (p < 0.001 and p < 0.01 for the comparison between NTg and PDAPP and NTg and PDAPP/HSF1, respectively, Bonferroni’s post hoc test applied to a significant effect of genotype, F(3,128) = 11.38, p < 0.0001, two-way anova), spatial learning in double-transgenic PDAPP/HSF1 mice was improved with respect to single-transgenic PDAPP mice in the last 2 days of training (p as indicated for the comparison between PDAPP and PDAPP/HSF1 groups, Welch’s correction on Student’s t-test. Welch’s correction was used because variances between PDAPP and PDAPP/HSF1 groups were significantly different, F(4,4) = 18.32, p = 0.01, F test). A significant interaction between day of training and performance for different genotypes was observed [F(12,128) = 2.79, p = 0.002]. Overall learning was effective [F(4,128) = 16.52, p < 0.0001, two-way anova] for all groups. (c) Time spent in the target quadrant in the probe trial was reduced in PDAPP mice with respect to non-transgenic littermates, as previously described (Chin et al. 2005; Galvan et al. 2006, 2008; Meilandt et al. 2009) (p value indicated, Welch’s correction on Student’s t-test). Time spent in the target quadrant was not significantly different between PDAPP and PDAPP/HSF1 groups. (d) Distance to the target (Gallagher proximity measure) was significantly larger for PDAPP mice with respect to all other experimental groups at all times during searching in a probe trial (p < 0.05, Tukey’s multiple comparison test applied to a significant effect of genotype on performance, p = 0.03, one-way anova). PDAPP/HSF1^+/0 animals, however, spent most of the trial time searching for the platform at locations closer to its former position, in a manner indistinguishable from non-transgenic or HSF1^+/0 single transgenic animals (p > 0.05 for both comparisons, p = 0.03, one-way anova). n = 8–18 animals/group. Data are means ± SEM.