Acquisition of conditioned taste aversion is impaired in the amyloid precursor protein/presenilin 1 mouse model of Alzheimer's disease - PubMed (original) (raw)

Acquisition of conditioned taste aversion is impaired in the amyloid precursor protein/presenilin 1 mouse model of Alzheimer's disease

P J Pistell et al. Neuroscience. 2008.

Abstract

Research into the underlying mechanisms of cognitive dysfunction in Alzheimer's disease (AD) has relied traditionally on tasks such as the water maze which evaluate spatial learning and memory. Since non-spatial forms of memory are also disrupted by AD, it is critical to establish other paradigms capable of investigating these deficits. Utilizing a non-spatial learning task, acquisition of conditioned taste aversion (CTA) was evaluated in a mouse model of AD. This line of transgenic mice encode a mutated allele of the human amyloid precursor protein (APP) and presenilin 1 (PS1) genes and exhibit extensive amyloid plaque deposition in the brain by 6-7 mo of age. Compared with wild-type mice, 10-17 month old APP/PS1 mice failed to acquire CTA to saccharin. Mice that only possessed one of the two mutations were able to acquire CTA to the saccharin. In 2-5 month old APP/PS1 mice acquisition of CTA was disrupted despite the lack of extensive plaque deposition. However, further analysis indicated a potential gender difference in both the CTA deficit and onset of plaque deposition with females showing greater conditioned aversion.

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Figures

Figure 1

Figure 1

A) Mean saccharin preference (+/- 1 s.e.m.) after LiCl or saline administration in older APP/PS1 and wildtype mice. B) Images of the hippocampus, amygdala and cortex from representative brains of 10-17 month old APP/PS1 and wildtype mice, stained with Congo red and counterstained with cresyl violet. The images were taken at 5X and then cropped with image editing software. The brains were examined visually and no quantitative analysis was conducted.

Figure 2

Figure 2

A) Mean saccharin preference (+/- 1 s.e.m.) after LiCl or saline administration in mice with either the mutation in APP (+/-) or PS1 (-/+). B) Images of the hippocampus, amygdala and cortex from representative brains of 9-17 month old APP (+/-) and PS1 (-/+), stained with Congo red and counterstained with cresyl violet. The images were taken at 5X and then cropped with image editing software.

Figure 3

Figure 3

A) Mean saccharin preference (+/- 1 s.e.m.) after LiCl administration in 2-5 month old APP/PS1 and wildtype mice. B) Images of the hippocampus, amygdala and cortex from representative brains of 2-5 month old APP/PS1 and wildtype mice, stained with Congo red and counterstained with cresyl violet. The images were taken at 5X and then cropped with image editing software. The brains were examined visually and no quantitative analysis was conducted.

Figure 4

Figure 4

A) Mean saccharin preference (+/- 1 s.e.m.) in 2-5 month old APP/PS1 and wildtype mice from experiment 3 broken into groups by gender and genotype. B) Mean saccharin preference (+/- 1 s.e.m.) in 10-17 month old APP/PS1 and wildtype mice from experiment 1 broken down into groups by gender and genotype.

Figure 5

Figure 5

Images of the hippocampus, amygdala and cortex from representative brains of 2-5 month old male and female APP/PS1 mice, stained with Congo red and counterstained with cresyl violet, showing the sporadic Aβ deposition present in some of the brains. The images were taken at 5X and then cropped with image editing software. The brains were examined visually and no quantitative analysis was conducted. Because the plaques were more difficult to visualize in black & white, for the younger mice, arrows indicate the presence and location of plaques.

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References

    1. Ashe KH. Synaptic structure and function in transgenic APP mice. Ann N Y Acad Sci. 2000;924:39–41. - PubMed
    1. Ashe KH. Learning and memory in transgenic mice modeling Alzheimer’s disease. Learn Mem. 2001;8:301–308. - PubMed
    1. Ashe KH. Mechanisms of memory loss in Abeta and tau mouse models. Biochem Soc Trans. 2005;33:591–594. - PubMed
    1. Best P, Orr J. Effects of hippocampal lesions on passive avoidance and taste aversion learning. Physiol Behav. 1973;10:193–196. - PubMed
    1. Borchelt DR, Ratovitski T, van Lare J, Lee MK, Gonzales V, Jenkins NA, Copeland NG, Price DL, Sisodia SS. Accelerated amyloid deposition in the brains of transgenic mice coexpressing mutant presenilin 1 and amyloid precursor proteins. Neuron. 1997;19:939–945. - PubMed

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