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Contribution of genetic and dietary insulin resistance to Alzheimer phenotype in APP/PS1 transgenic mice.

Hiltunen M, Khandelwal VK, Yaluri N, Tiilikainen T, Tusa M, Koivisto H, Krzisch M, Vepsäläinen S, Mäkinen P, Kemppainen S, Miettinen P, Haapasalo A, Soininen H, Laakso M, Tanila H - J. Cell. Mol. Med. (2012)

Bottom Line: According to epidemiological studies, type-2 diabetes increases the risk of Alzheimer's disease.Neither high-fat diet nor IGF-2 increased β-amyloid burden in the brain.These findings provide evidence for new regulatory mechanisms that link type-2 diabetes and Alzheimer pathology.

View Article: PubMed Central - PubMed

Affiliation: Institute of Clinical Medicine - Neurology, University of Eastern Finland, Kuopio, Finland. mikko.hiltunen@uef.fi

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Summary of behavioural tests in mice on standard diet (STD) or high-fat diet (TWD). Ambulatory distance (gross horizontal locomotion) in a new test cage during 10 min. in (A) IGF-2 wild-type (Iw) and (B) IGF-2 transgenic (I+) female mice. Escape latency to reach the hidden platform in the Morris swim navigation task in (C) IGF-2 wild-type (Iw) and (D) IGF-2 transgenic (I+) female mice at 8 months of age. Corresponding data are shown for (E) IGF-2 wild-type (Iw) and (F) IGF-2 transgenic (I+) male mice at 12 months of age. Note the impairment in A+I+ mice on TWD groups in both genders. A probe trial on day 6 tests memory for the platform location in terms of time spent in the target quadrant of the pool. (G) Among female mice, only AwIw mice independent of diet show a significant search bias, whereas (H) AwIw and AwI+ male mice on STD search in the correct target quadrant. The dashed line indicates probability of a random search. S: standard diet; T: typical Western diet; n ∇ 4–6 mice/group.
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fig03: Summary of behavioural tests in mice on standard diet (STD) or high-fat diet (TWD). Ambulatory distance (gross horizontal locomotion) in a new test cage during 10 min. in (A) IGF-2 wild-type (Iw) and (B) IGF-2 transgenic (I+) female mice. Escape latency to reach the hidden platform in the Morris swim navigation task in (C) IGF-2 wild-type (Iw) and (D) IGF-2 transgenic (I+) female mice at 8 months of age. Corresponding data are shown for (E) IGF-2 wild-type (Iw) and (F) IGF-2 transgenic (I+) male mice at 12 months of age. Note the impairment in A+I+ mice on TWD groups in both genders. A probe trial on day 6 tests memory for the platform location in terms of time spent in the target quadrant of the pool. (G) Among female mice, only AwIw mice independent of diet show a significant search bias, whereas (H) AwIw and AwI+ male mice on STD search in the correct target quadrant. The dashed line indicates probability of a random search. S: standard diet; T: typical Western diet; n ∇ 4–6 mice/group.

Mentions: Female mice underwent neurological testing at the age of 8 months and male mice at the age of 12 months. Female APdE9-positive mice exhibited hyperactivity in a new environment [F(1,68) ∇ 18.4, P < 0.001]. However, this was dependent on the IGF-2 genotype (F ∇ 4.7, P ∇ 0.03), so that I+ mice were not hyperactive compared to IwAw mice on STD (Fig. 3A and B). Among male mice, the APdE9 genotype had little effect on exploratory activity (Fig. 3E and F). On the other hand, the effect of diet approached significance in male mice [F(1,66) ∇ 3.6, P ∇ 0.06], as all mice on TWD, except the A+I+ mice, moved less than the mice on STD (Fig. 3E and F). Spatial learning was assessed with the Morris swim navigation task. Among 8-month-old female mice, APdE9-positive mice, as expected, were inferior in the task than APdE9 non-transgenic mice (Fig. 3C and D). However, the effect of the APdE9 transgene on escape latency only approached significance [F(1,67) ∇ 3.1, P ∇ 0.08]. In contrast, there was a significant IGF-2 χ diet interaction (F ∇ 4.3, P ∇ 0.04). TWD did not affect learning in IwAw or IwA+ mice but it had a deleterious effect in I+Aw or I+A+ mice (Fig. 3C and D). The genotypes or the diet did not significantly modulate swimming speed, so escape latency can be taken as a valid measure of the task acquisition.


Contribution of genetic and dietary insulin resistance to Alzheimer phenotype in APP/PS1 transgenic mice.

Hiltunen M, Khandelwal VK, Yaluri N, Tiilikainen T, Tusa M, Koivisto H, Krzisch M, Vepsäläinen S, Mäkinen P, Kemppainen S, Miettinen P, Haapasalo A, Soininen H, Laakso M, Tanila H - J. Cell. Mol. Med. (2012)

Summary of behavioural tests in mice on standard diet (STD) or high-fat diet (TWD). Ambulatory distance (gross horizontal locomotion) in a new test cage during 10 min. in (A) IGF-2 wild-type (Iw) and (B) IGF-2 transgenic (I+) female mice. Escape latency to reach the hidden platform in the Morris swim navigation task in (C) IGF-2 wild-type (Iw) and (D) IGF-2 transgenic (I+) female mice at 8 months of age. Corresponding data are shown for (E) IGF-2 wild-type (Iw) and (F) IGF-2 transgenic (I+) male mice at 12 months of age. Note the impairment in A+I+ mice on TWD groups in both genders. A probe trial on day 6 tests memory for the platform location in terms of time spent in the target quadrant of the pool. (G) Among female mice, only AwIw mice independent of diet show a significant search bias, whereas (H) AwIw and AwI+ male mice on STD search in the correct target quadrant. The dashed line indicates probability of a random search. S: standard diet; T: typical Western diet; n ∇ 4–6 mice/group.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3823075&req=5

fig03: Summary of behavioural tests in mice on standard diet (STD) or high-fat diet (TWD). Ambulatory distance (gross horizontal locomotion) in a new test cage during 10 min. in (A) IGF-2 wild-type (Iw) and (B) IGF-2 transgenic (I+) female mice. Escape latency to reach the hidden platform in the Morris swim navigation task in (C) IGF-2 wild-type (Iw) and (D) IGF-2 transgenic (I+) female mice at 8 months of age. Corresponding data are shown for (E) IGF-2 wild-type (Iw) and (F) IGF-2 transgenic (I+) male mice at 12 months of age. Note the impairment in A+I+ mice on TWD groups in both genders. A probe trial on day 6 tests memory for the platform location in terms of time spent in the target quadrant of the pool. (G) Among female mice, only AwIw mice independent of diet show a significant search bias, whereas (H) AwIw and AwI+ male mice on STD search in the correct target quadrant. The dashed line indicates probability of a random search. S: standard diet; T: typical Western diet; n ∇ 4–6 mice/group.
Mentions: Female mice underwent neurological testing at the age of 8 months and male mice at the age of 12 months. Female APdE9-positive mice exhibited hyperactivity in a new environment [F(1,68) ∇ 18.4, P < 0.001]. However, this was dependent on the IGF-2 genotype (F ∇ 4.7, P ∇ 0.03), so that I+ mice were not hyperactive compared to IwAw mice on STD (Fig. 3A and B). Among male mice, the APdE9 genotype had little effect on exploratory activity (Fig. 3E and F). On the other hand, the effect of diet approached significance in male mice [F(1,66) ∇ 3.6, P ∇ 0.06], as all mice on TWD, except the A+I+ mice, moved less than the mice on STD (Fig. 3E and F). Spatial learning was assessed with the Morris swim navigation task. Among 8-month-old female mice, APdE9-positive mice, as expected, were inferior in the task than APdE9 non-transgenic mice (Fig. 3C and D). However, the effect of the APdE9 transgene on escape latency only approached significance [F(1,67) ∇ 3.1, P ∇ 0.08]. In contrast, there was a significant IGF-2 χ diet interaction (F ∇ 4.3, P ∇ 0.04). TWD did not affect learning in IwAw or IwA+ mice but it had a deleterious effect in I+Aw or I+A+ mice (Fig. 3C and D). The genotypes or the diet did not significantly modulate swimming speed, so escape latency can be taken as a valid measure of the task acquisition.

Bottom Line: According to epidemiological studies, type-2 diabetes increases the risk of Alzheimer's disease.Neither high-fat diet nor IGF-2 increased β-amyloid burden in the brain.These findings provide evidence for new regulatory mechanisms that link type-2 diabetes and Alzheimer pathology.

View Article: PubMed Central - PubMed

Affiliation: Institute of Clinical Medicine - Neurology, University of Eastern Finland, Kuopio, Finland. mikko.hiltunen@uef.fi

Show MeSH
Related in: MedlinePlus