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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

Activity chamber. (a) Activity was monitored for 10 min in the activity chamber (upper panel). Display of tracks of median Thy1-hAPPLond/Swe+ and control mouse (lower panels). (b) Thy1-hAPPLond/Swe+ traveled a longer distance than control mice (P = 0.0004, repeated measures ANOVA). (c) Correspondingly, Thy1-hAPPLond/Swe+ traveled a longer cumulative distance than control mice (P < 0.01, t-test). (d) Both groups of mice traveled a longer distance in the periphery, but this effect did not differ significantly by genotype (genotype × zone interaction: F1, 21 = 2.33, P = 0.14). (e) Mutant mice spent proportionally more time in the periphery than the center compared to control mice, but this difference was not statistically significant different between genotypes (genotype × zone interaction: F1, 21 = 2.82, P = 0.11). (f) Mutant mice reared significantly more than control mice in a minute-to-minute comparison (P < 0.05, repeated measures ANOVA) (g) and correspondingly exhibited more total rearings (P < 0.05, t-test). n(control) = 12, n(Thy1-hAPPLond/Swe+) = 11.
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fig01: Activity chamber. (a) Activity was monitored for 10 min in the activity chamber (upper panel). Display of tracks of median Thy1-hAPPLond/Swe+ and control mouse (lower panels). (b) Thy1-hAPPLond/Swe+ traveled a longer distance than control mice (P = 0.0004, repeated measures ANOVA). (c) Correspondingly, Thy1-hAPPLond/Swe+ traveled a longer cumulative distance than control mice (P < 0.01, t-test). (d) Both groups of mice traveled a longer distance in the periphery, but this effect did not differ significantly by genotype (genotype × zone interaction: F1, 21 = 2.33, P = 0.14). (e) Mutant mice spent proportionally more time in the periphery than the center compared to control mice, but this difference was not statistically significant different between genotypes (genotype × zone interaction: F1, 21 = 2.82, P = 0.11). (f) Mutant mice reared significantly more than control mice in a minute-to-minute comparison (P < 0.05, repeated measures ANOVA) (g) and correspondingly exhibited more total rearings (P < 0.05, t-test). n(control) = 12, n(Thy1-hAPPLond/Swe+) = 11.

Mentions: Exploratory behavior in a novel environment and general locomotor activity were assessed in automated activity chambers for 10 min (Fig. 1a). Median tracks of Thy1-hAPPLond/Swe+ and control littermates are shown in Figure 1a. A minute-to-minute analysis revealed that Thy1-hAPPLond/Swe+ mice consistently moved a longer distance than their control littermates (Fig. 1b; effect of genotype, F1, 21 = 17.54, P = 0.0004; genotype × time interaction, F9, 189 = 0.93, P = 0.50). Accordingly, the total (cumulative) distance moved in the novel environment was significantly higher in Thy1-hAPPLond/Swe+ than in control mice (Fig. 1c; P = 0.0016). Both groups of mice showed higher activity in the perhipheral zone than in the central zone both in terms of the distance moved (Fig. 1d; effect of zone, F1, 21 = 59.25, P < 0.0001) and the time spent in the two zones (Fig. 1e; effect of zone, F1, 21 = 140.3, P < 0.0001). Thy1-hAPPLond/Swe+ mice tended to show more activity in the peripheral zone than the control mice; however, the genotype × zone interaction did not achieve statistical significance for either distance moved (genotype × zone interaction, F1, 21 = 2.33, P = 0.14) or time spent in zones (genotype × zone interaction: F1, 21 = 2.82, P = 0.11). Thy1-hAPPLond/Swe+ mice engaged in significantly more rearing behavior than their control littermates (Fig. 1f, 1g; effect of genotype, F1, 21 = 4.68, P = 0.042).


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)

Activity chamber. (a) Activity was monitored for 10 min in the activity chamber (upper panel). Display of tracks of median Thy1-hAPPLond/Swe+ and control mouse (lower panels). (b) Thy1-hAPPLond/Swe+ traveled a longer distance than control mice (P = 0.0004, repeated measures ANOVA). (c) Correspondingly, Thy1-hAPPLond/Swe+ traveled a longer cumulative distance than control mice (P < 0.01, t-test). (d) Both groups of mice traveled a longer distance in the periphery, but this effect did not differ significantly by genotype (genotype × zone interaction: F1, 21 = 2.33, P = 0.14). (e) Mutant mice spent proportionally more time in the periphery than the center compared to control mice, but this difference was not statistically significant different between genotypes (genotype × zone interaction: F1, 21 = 2.82, P = 0.11). (f) Mutant mice reared significantly more than control mice in a minute-to-minute comparison (P < 0.05, repeated measures ANOVA) (g) and correspondingly exhibited more total rearings (P < 0.05, t-test). n(control) = 12, n(Thy1-hAPPLond/Swe+) = 11.
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fig01: Activity chamber. (a) Activity was monitored for 10 min in the activity chamber (upper panel). Display of tracks of median Thy1-hAPPLond/Swe+ and control mouse (lower panels). (b) Thy1-hAPPLond/Swe+ traveled a longer distance than control mice (P = 0.0004, repeated measures ANOVA). (c) Correspondingly, Thy1-hAPPLond/Swe+ traveled a longer cumulative distance than control mice (P < 0.01, t-test). (d) Both groups of mice traveled a longer distance in the periphery, but this effect did not differ significantly by genotype (genotype × zone interaction: F1, 21 = 2.33, P = 0.14). (e) Mutant mice spent proportionally more time in the periphery than the center compared to control mice, but this difference was not statistically significant different between genotypes (genotype × zone interaction: F1, 21 = 2.82, P = 0.11). (f) Mutant mice reared significantly more than control mice in a minute-to-minute comparison (P < 0.05, repeated measures ANOVA) (g) and correspondingly exhibited more total rearings (P < 0.05, t-test). n(control) = 12, n(Thy1-hAPPLond/Swe+) = 11.
Mentions: Exploratory behavior in a novel environment and general locomotor activity were assessed in automated activity chambers for 10 min (Fig. 1a). Median tracks of Thy1-hAPPLond/Swe+ and control littermates are shown in Figure 1a. A minute-to-minute analysis revealed that Thy1-hAPPLond/Swe+ mice consistently moved a longer distance than their control littermates (Fig. 1b; effect of genotype, F1, 21 = 17.54, P = 0.0004; genotype × time interaction, F9, 189 = 0.93, P = 0.50). Accordingly, the total (cumulative) distance moved in the novel environment was significantly higher in Thy1-hAPPLond/Swe+ than in control mice (Fig. 1c; P = 0.0016). Both groups of mice showed higher activity in the perhipheral zone than in the central zone both in terms of the distance moved (Fig. 1d; effect of zone, F1, 21 = 59.25, P < 0.0001) and the time spent in the two zones (Fig. 1e; effect of zone, F1, 21 = 140.3, P < 0.0001). Thy1-hAPPLond/Swe+ mice tended to show more activity in the peripheral zone than the control mice; however, the genotype × zone interaction did not achieve statistical significance for either distance moved (genotype × zone interaction, F1, 21 = 2.33, P = 0.14) or time spent in zones (genotype × zone interaction: F1, 21 = 2.82, P = 0.11). Thy1-hAPPLond/Swe+ mice engaged in significantly more rearing behavior than their control littermates (Fig. 1f, 1g; effect of genotype, F1, 21 = 4.68, P = 0.042).

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