Table 1.
Experimental groups.
Fig 1.
Representative images of (A) DCX staining (2.5x objective), (B) PSD95 staining (2.5x objective). Black = visual cortex, white = sensory cortex, yellow = stratum radiatum, blue = inner molecular layer, red = outer molecular layer, green = stratum lucidum, (C) GLUT-1 staining (5x objective), and (D) CD68 staining (5x objective). Scale bars represent 500μm.
Fig 2.
Body weight during the experimental phase.
HF diet increased body weight pre- and post-testing in both ApoE4 (p<0.001) and WT (p<0.001) mice compared to CTRL diet, but not in ApoE-/-. Furthermore, the body weight increase due to HF diet was significantly stronger in ApoE4 compared to WT (p = 0.002). Values represent mean±SEM; WT CTRL n = 8, WT HF n = 8, ApoE4 CTRL n = 8, ApoE4 HF n = 8, ApoE-/- CTRL n = 5, ApoE-/- HF n = 6. *p≤0.05. ApoE = apolipoprotein E; CTRL = control; HF = high-fat; WT = wild-type.
Table 2.
Brain weights for immunohistochemistry.
Fig 3.
MWM acquisition and probe (0-30s).
(A) Both groups displayed a learning effect (p = 0.000). HF fed mice showed improved spatial learning compared to CTRL diet (p = 0.045). (B) Both groups displayed a learning effect (p = 0.000). ApoE-/- demonstrated improved spatial learning compared to WT mice (p = 0.009). There was no difference in spatial learning between diets. (C) No significant differences were found in the probe phase of the MWM caused by either genotype or diet (p>0.05). (D) No significant differences were found in the probe phase of the MWM caused by either genotype or diet (p>0.05). ApoE-/- mice displayed a trend for increased time spent in platform area (p = 0.059). Values represent mean±SEM; WT CTRL n = 6, WT HF n = 7, ApoE4 CTRL n = 8, ApoE4 HF n = 8, ApoE-/- CTRL n = 6, ApoE-/- HF n = 6. *p≤0.05. ApoE = apolipoprotein E; CTRL = control; HF = high-fat; MWM = Morris water maze; WT = wild-type.
Fig 4.
In the CA1, we observed a genotype × diet interaction (p = 0.001), there was a trend for increased inflammation in WT after HF supplementation (p = 0.052). Inflammation in ApoE4 mice significantly decreased after HF supplementation (p = 0.009). ApoE4 mice on CTRL demonstrated increased inflammation compared to WT mice on CTRL (p = 0.001). ApoE-/- compared to WT mice showed a genotype × diet interaction (p = 0.010). ApoE-/- on CTRL demonstrated increased inflammation when compared to WT mice on CTRL (p = 0.032). In the CA3, a genotype × diet interaction was observed (p = 0.024) but no significant effect on inflammation caused by genotype or diet when comparing ApoE4 to WT mice. Furthermore, ApoE-/- compared to WT mice showed a genotype × diet interaction (p = 0.023). No significant effects on inflammation caused by genotype or diet were found though. In the DG, we observed a genotype × diet interaction (p = 0.047) when comparing ApoE4 to WT mice. There was a trend for increased inflammation in ApoE4 mice on CTRL diet compared to WT mice on CTRL (p = 0.063). In addition, ApoE-/- displayed increased inflammation when compared to WT mice (p = 0.029). Values represent mean±SEM; WT CTRL n = 5, WT HF n = 7, ApoE4 CTRL n = 7, ApoE4 HF n = 5, ApoE-/- CTRL n = 4, ApoE-/- HF n = 6. *p≤0.05, #0.05<p<0.07. ApoE = apolipoprotein E; CA1 = cornu ammonis 1; CA3 = cornu ammonis 3; CD68 = cluster of differentiation 68; CTRL = control; DG = dentate gyrus; HF = high-fat; WT = wild-type.
Fig 5.
ApoE4 and ApoE-/- mice display a trend for increased adult neurogenesis compared to WT mice (p = 0.052 and p = 0.068 respectively). Values represent mean±SEM; WT CTRL n = 4, WT HF n = 6, ApoE4 CTRL n = 4, ApoE4 HF n = 7, ApoE-/- CTRL n = 4, ApoE-/- HF n = 7. #0.05<p<0.07. ApoE = apolipoprotein E; CTRL = control; DCX = doublecortin; DG = dentate gyrus; HF = high-fat; WT = wild-type.
Fig 6.
PSD95 was analyzed as a synaptic marker in the VIS, SEN, IML, OML, SL and SR of the hippocampus. No significant genotype nor diet effects were found (p>0.05). In the SEN, ApoE-/- mice showed a slight trend (p = 0.064) for decreased PSD95 expression. Values represent mean±SEM; WT CTRL n = 8, WT HF n = 8, ApoE4 CTRL n = 8, ApoE4 HF n = 7, ApoE-/- CTRL n = 5, ApoE-/- HF n = 7. #0.05<p<0.07. ApoE = apolipoprotein E; CTRL = control; HF = high-fat; IML = inner molecular layer; OML = outer molecular layer; PSD = post-synaptic density; SEN = sensory cortex; SL = stratum lucidum; SR = stratum radiatum; VIS = visual cortex; WT = wild-type.
Fig 7.
GLUT-1 density was analyzed as a measure for capillary density. No differences in capillary density, caused by either genotype nor diet, were observed (p>0.05). Values represent mean±SEM; WT CTRL n = 6, WT HF n = 6, ApoE4 CTRL n = 6, ApoE4 HF n = 6, ApoE-/- CTRL n = 4, ApoE-/- HF n = 4. ApoE = apolipoprotein E; CA1 = cornu ammonis 1; CA3 = cornu ammonis 3; CTRL = control; DG = dentate gyrus; GLUT = glucose transporter; HF = high-fat; WT = wild-type.