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Thy1-hAPP(Lond/Swe+) mouse model of Alzheimer's disease displays broad behavioral deficits in sensorimotor, cognitive and social function.

Faizi M, Bader PL, Saw N, Nguyen TV, Beraki S, Wyss-Coray T, Longo FM, Shamloo M - Brain Behav (2012)

Bottom Line: We found hyperactivity in a novel environment as well as significant deficits in spontaneous alternation behavior.This could possibly be explained by decreased social memory or discrimination and may parallel disturbances in social functioning in human AD patients.In conclusion, the Thy1-hAPP(Lond/Swe+) mouse model of AD displayed a behavioral phenotype that resembles, in part, the cognitive and psychiatric symptoms experienced in AD patients.

View Article: PubMed Central - PubMed

ABSTRACT
Alzheimer's disease (AD), the most common form of dementia, is an age-dependent progressive neurodegenerative disorder. β-amyloid, a metabolic product of the amyloid precursor protein (APP), plays an important role in the pathogenesis of AD. The Thy1-hAPP(Lond/Swe+) (line 41) transgenic mouse overexpresses human APP751 and contains the London (V717I) and Swedish (K670M/N671L) mutations. Here, we used a battery of behavioral tests to evaluate general activity, cognition, and social behavior in six-month-old male Thy1-hAPP(Lond/Swe+) mice. We found hyperactivity in a novel environment as well as significant deficits in spontaneous alternation behavior. In fear conditioning (FC), Thy1-hAPP(Lond/Swe+) mice did not display deficits in acquisition or in memory retrieval in novel context of tone-cued FC, but they showed significant memory retrieval impairment during contextual testing in an identical environment. Surprisingly, in a standard hidden platform water maze, no significant deficit was detected in mutant mice. However, a delayed-matching-to-place paradigm revealed a significant deficit in Thy1-hAPP(Lond/Swe+) mice. Lastly, in the social novelty session of a three-chamber test, Thy1-hAPP(Lond/Swe+) mice exhibited a significantly decreased interest in a novel versus a familiar stranger compared to control mice. This could possibly be explained by decreased social memory or discrimination and may parallel disturbances in social functioning in human AD patients. In conclusion, the Thy1-hAPP(Lond/Swe+) mouse model of AD displayed a behavioral phenotype that resembles, in part, the cognitive and psychiatric symptoms experienced in AD patients.

No MeSH data available.


Related in: MedlinePlus

Open field. (a) Activity levels were measured in a 10-min open field test (upper panel). Tracks of median Thy1-hAPPLond/Swe+ and control mice are displayed in the lower panels. (b) Thy1-hAPPLond/Swe+ mice traveled a significantly longer distance than control mice (P < 0.01, repeated-measures ANOVA) (c) and, correspondingly a longer total distance (P < 0.01, t-test). (d). Both genotypes traveled a longer distance in the periphery than the center and the effect of zone was more pronounced in mutant mice (genotype x zone interaction, P = 0.004; Bonferroni post-hoc tests: P < 0.001 and P > 0.05, respectively). (e) Similarly, mice spent significantly more time in the center zone but in this case the effect was not different between genotypes (genotype x zone interaction, P = 0.28). n(control) = 12, n(Thy1-hAPPLond/Swe+) = 11.
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fig02: Open field. (a) Activity levels were measured in a 10-min open field test (upper panel). Tracks of median Thy1-hAPPLond/Swe+ and control mice are displayed in the lower panels. (b) Thy1-hAPPLond/Swe+ mice traveled a significantly longer distance than control mice (P < 0.01, repeated-measures ANOVA) (c) and, correspondingly a longer total distance (P < 0.01, t-test). (d). Both genotypes traveled a longer distance in the periphery than the center and the effect of zone was more pronounced in mutant mice (genotype x zone interaction, P = 0.004; Bonferroni post-hoc tests: P < 0.001 and P > 0.05, respectively). (e) Similarly, mice spent significantly more time in the center zone but in this case the effect was not different between genotypes (genotype x zone interaction, P = 0.28). n(control) = 12, n(Thy1-hAPPLond/Swe+) = 11.

Mentions: The open-field test was used for assessment of gross locomotor activity and exploration behavior in a relatively large novel environment as compared to the activity chamber (Fig. 2a). Thy1-hAPPLond/Swe+ mice moved a longer distance in the open field compared with control animals (Fig. 2b and 2c; effect of genotype, F1, 21 = 9.10, P = 0.007; genotype × time interaction, F9, 189 = 0.80, P = 0.61) and showed a significantly increased velocity (control: 9.26 ± 0.24 cm/s; mutant: 11.03 ± 0.35 cm/s; P = 0.006). Both genotypes moved a longer distance in the periphery zone than the center zone (Fig. 2d; effect of zone, F1, 21 = 934.6, P < 0.0001), but the effect of zone was more pronounced in the Thy1-hAPPLond/Swe+ mice (genotype × zone interaction, F1, 21 = 10.62, P = 0.004). Mice spent more time in the center zone (Fig. 2e; effect of zone, F1, 21 = 3064.92, P < 0.0001) but this effect was not different between genotypes (genotype × zone interaction, F1, 21 = 1.21, P = 0.28).


Thy1-hAPP(Lond/Swe+) mouse model of Alzheimer's disease displays broad behavioral deficits in sensorimotor, cognitive and social function.

Faizi M, Bader PL, Saw N, Nguyen TV, Beraki S, Wyss-Coray T, Longo FM, Shamloo M - Brain Behav (2012)

Open field. (a) Activity levels were measured in a 10-min open field test (upper panel). Tracks of median Thy1-hAPPLond/Swe+ and control mice are displayed in the lower panels. (b) Thy1-hAPPLond/Swe+ mice traveled a significantly longer distance than control mice (P < 0.01, repeated-measures ANOVA) (c) and, correspondingly a longer total distance (P < 0.01, t-test). (d). Both genotypes traveled a longer distance in the periphery than the center and the effect of zone was more pronounced in mutant mice (genotype x zone interaction, P = 0.004; Bonferroni post-hoc tests: P < 0.001 and P > 0.05, respectively). (e) Similarly, mice spent significantly more time in the center zone but in this case the effect was not different between genotypes (genotype x zone interaction, P = 0.28). n(control) = 12, n(Thy1-hAPPLond/Swe+) = 11.
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC3345358&req=5

fig02: Open field. (a) Activity levels were measured in a 10-min open field test (upper panel). Tracks of median Thy1-hAPPLond/Swe+ and control mice are displayed in the lower panels. (b) Thy1-hAPPLond/Swe+ mice traveled a significantly longer distance than control mice (P < 0.01, repeated-measures ANOVA) (c) and, correspondingly a longer total distance (P < 0.01, t-test). (d). Both genotypes traveled a longer distance in the periphery than the center and the effect of zone was more pronounced in mutant mice (genotype x zone interaction, P = 0.004; Bonferroni post-hoc tests: P < 0.001 and P > 0.05, respectively). (e) Similarly, mice spent significantly more time in the center zone but in this case the effect was not different between genotypes (genotype x zone interaction, P = 0.28). n(control) = 12, n(Thy1-hAPPLond/Swe+) = 11.
Mentions: The open-field test was used for assessment of gross locomotor activity and exploration behavior in a relatively large novel environment as compared to the activity chamber (Fig. 2a). Thy1-hAPPLond/Swe+ mice moved a longer distance in the open field compared with control animals (Fig. 2b and 2c; effect of genotype, F1, 21 = 9.10, P = 0.007; genotype × time interaction, F9, 189 = 0.80, P = 0.61) and showed a significantly increased velocity (control: 9.26 ± 0.24 cm/s; mutant: 11.03 ± 0.35 cm/s; P = 0.006). Both genotypes moved a longer distance in the periphery zone than the center zone (Fig. 2d; effect of zone, F1, 21 = 934.6, P < 0.0001), but the effect of zone was more pronounced in the Thy1-hAPPLond/Swe+ mice (genotype × zone interaction, F1, 21 = 10.62, P = 0.004). Mice spent more time in the center zone (Fig. 2e; effect of zone, F1, 21 = 3064.92, P < 0.0001) but this effect was not different between genotypes (genotype × zone interaction, F1, 21 = 1.21, P = 0.28).

Bottom Line: We found hyperactivity in a novel environment as well as significant deficits in spontaneous alternation behavior.This could possibly be explained by decreased social memory or discrimination and may parallel disturbances in social functioning in human AD patients.In conclusion, the Thy1-hAPP(Lond/Swe+) mouse model of AD displayed a behavioral phenotype that resembles, in part, the cognitive and psychiatric symptoms experienced in AD patients.

View Article: PubMed Central - PubMed

ABSTRACT
Alzheimer's disease (AD), the most common form of dementia, is an age-dependent progressive neurodegenerative disorder. β-amyloid, a metabolic product of the amyloid precursor protein (APP), plays an important role in the pathogenesis of AD. The Thy1-hAPP(Lond/Swe+) (line 41) transgenic mouse overexpresses human APP751 and contains the London (V717I) and Swedish (K670M/N671L) mutations. Here, we used a battery of behavioral tests to evaluate general activity, cognition, and social behavior in six-month-old male Thy1-hAPP(Lond/Swe+) mice. We found hyperactivity in a novel environment as well as significant deficits in spontaneous alternation behavior. In fear conditioning (FC), Thy1-hAPP(Lond/Swe+) mice did not display deficits in acquisition or in memory retrieval in novel context of tone-cued FC, but they showed significant memory retrieval impairment during contextual testing in an identical environment. Surprisingly, in a standard hidden platform water maze, no significant deficit was detected in mutant mice. However, a delayed-matching-to-place paradigm revealed a significant deficit in Thy1-hAPP(Lond/Swe+) mice. Lastly, in the social novelty session of a three-chamber test, Thy1-hAPP(Lond/Swe+) mice exhibited a significantly decreased interest in a novel versus a familiar stranger compared to control mice. This could possibly be explained by decreased social memory or discrimination and may parallel disturbances in social functioning in human AD patients. In conclusion, the Thy1-hAPP(Lond/Swe+) mouse model of AD displayed a behavioral phenotype that resembles, in part, the cognitive and psychiatric symptoms experienced in AD patients.

No MeSH data available.


Related in: MedlinePlus