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Early enriched environment exposure protects spatial memory and accelerates amyloid plaque formation in APP(Swe)/PS1(L166P) mice.

Montarolo F, Parolisi R, Hoxha E, Boda E, Tempia F - PLoS ONE (2013)

Bottom Line: On the other hand, chronic neuronal activity suppression by tetrodotoxin decreased the number of plaques without affecting intracellular amyloid.These results indicate that enriched environment exposure since early life has a protective effect on cognitive deterioration although transiently accelerates amyloid deposition.In addition, the effects of the enriched environment might be due to increased neuronal activity, because plaques were reduced by suppression of electrical signaling by tetrodotoxin.

View Article: PubMed Central - PubMed

Affiliation: Institute Cavalieri Ottolenghi (NICO), University of Torino, Orbassano (Torino), Italy.

ABSTRACT
Enriched environment exposure improves several aspects of cognitive performance in Alzheimer's disease patients and in animal models and, although the role of amyloid plaques is questionable, several studies also assessed their response to enriched environment, with contrasting results. Here we report that rearing APP(Swe)/PS1(L166P) mice in an enriched environment since birth rescued the spatial memory impairment otherwise present at 6 months of age. At the same time, the exposure to the enriched environment caused a transient acceleration of plaque formation, while there was no effect on intracellular staining with the 6E10 antibody, which recognizes β-amyloid, full length amyloid precursor protein and its C-terminal fragments. The anticipation of plaque formation required exposure during early development, suggesting an action within critical periods for circuits formation. On the other hand, chronic neuronal activity suppression by tetrodotoxin decreased the number of plaques without affecting intracellular amyloid. These results indicate that enriched environment exposure since early life has a protective effect on cognitive deterioration although transiently accelerates amyloid deposition. In addition, the effects of the enriched environment might be due to increased neuronal activity, because plaques were reduced by suppression of electrical signaling by tetrodotoxin.

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EE reduces the performance deficits of APPSwe/PS1L166P mice in the Morris water maze.Average spatial memory performance during the acquisition phase expressed as escape latency over four daily sessions of four consecutive trials in 2- (A), 4- (C) and 6- (E) month-old APPSwe/PS1L166P mice housed in SE or EE (n = 8 in each group, * P<0.05 housing condition effect, Two-way Repeated-Measures ANOVA). Average accuracy ratio of 2- (B), 4- (D) and 6- (F) month-old APPSwe/PS1L166P mice housed in SE and in EE, tested in the probe trial 24 h after the last acquisition session (day 5) (n = 8 in each group, * P<0.05, Student’s t-test). Error bars represent SEM. (APPSwe/PS1L166P SE, APPSwe/PS1L166P mice housed in Standard Environment; APPSwe/PS1L166P EE, APPSwe/PS1L166P mice housed in Enriched Environment).
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pone-0069381-g007: EE reduces the performance deficits of APPSwe/PS1L166P mice in the Morris water maze.Average spatial memory performance during the acquisition phase expressed as escape latency over four daily sessions of four consecutive trials in 2- (A), 4- (C) and 6- (E) month-old APPSwe/PS1L166P mice housed in SE or EE (n = 8 in each group, * P<0.05 housing condition effect, Two-way Repeated-Measures ANOVA). Average accuracy ratio of 2- (B), 4- (D) and 6- (F) month-old APPSwe/PS1L166P mice housed in SE and in EE, tested in the probe trial 24 h after the last acquisition session (day 5) (n = 8 in each group, * P<0.05, Student’s t-test). Error bars represent SEM. (APPSwe/PS1L166P SE, APPSwe/PS1L166P mice housed in Standard Environment; APPSwe/PS1L166P EE, APPSwe/PS1L166P mice housed in Enriched Environment).

Mentions: Most notably EE completely reverted the spatial memory deficit displayed by 6-month-old APPSwe/PS1L166P mice reared in SE (Fig. 7). In fact, after 6 months spent in EE, APPSwe/PS1L166P mice significantly improved their performance (Two-way Repeated-Measures ANOVA, housing condition effect, P<0.05; day effect, P<0.001). The post-hoc test revealed that, since the second day of training, APPSwe/PS1L166P mice reared in EE spent significantly less time to reach the submerged platform relative to those which lived in SE (escape latency for APPSwe/PS1L166P mice 65.08±4.54 s in SE, 39.95±7.51 s in EE; Bonferroni, P<0.05). The memory deficit reversal in 6-month-old APPSwe/PS1L166P mice reared in EE was confirmed by a significant improvement in AR relative to SE mice, with an increase from the chance level of about 1 to a value greater than 3 (Fig. 7; Student’s t-test, P<0.05). On the contrary, in 2- and 4-month-old APPSwe/PS1L166P mice, the AR was higher than chance level in both SE and EE groups, without any significant difference between the two housing conditions (Fig. 7B, D; Student’s t-test, P>0.05). The effect of EE on the escape latency cannot be attributed to other factors like swimming velocity or distance covered, because these parameters showed significant differences neither between genotypes nor between caging conditions at any analyzed time point, suggesting equivalent vision, locomotor skills, and motivation (data not shown).


Early enriched environment exposure protects spatial memory and accelerates amyloid plaque formation in APP(Swe)/PS1(L166P) mice.

Montarolo F, Parolisi R, Hoxha E, Boda E, Tempia F - PLoS ONE (2013)

EE reduces the performance deficits of APPSwe/PS1L166P mice in the Morris water maze.Average spatial memory performance during the acquisition phase expressed as escape latency over four daily sessions of four consecutive trials in 2- (A), 4- (C) and 6- (E) month-old APPSwe/PS1L166P mice housed in SE or EE (n = 8 in each group, * P<0.05 housing condition effect, Two-way Repeated-Measures ANOVA). Average accuracy ratio of 2- (B), 4- (D) and 6- (F) month-old APPSwe/PS1L166P mice housed in SE and in EE, tested in the probe trial 24 h after the last acquisition session (day 5) (n = 8 in each group, * P<0.05, Student’s t-test). Error bars represent SEM. (APPSwe/PS1L166P SE, APPSwe/PS1L166P mice housed in Standard Environment; APPSwe/PS1L166P EE, APPSwe/PS1L166P mice housed in Enriched Environment).
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Related In: Results  -  Collection

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pone-0069381-g007: EE reduces the performance deficits of APPSwe/PS1L166P mice in the Morris water maze.Average spatial memory performance during the acquisition phase expressed as escape latency over four daily sessions of four consecutive trials in 2- (A), 4- (C) and 6- (E) month-old APPSwe/PS1L166P mice housed in SE or EE (n = 8 in each group, * P<0.05 housing condition effect, Two-way Repeated-Measures ANOVA). Average accuracy ratio of 2- (B), 4- (D) and 6- (F) month-old APPSwe/PS1L166P mice housed in SE and in EE, tested in the probe trial 24 h after the last acquisition session (day 5) (n = 8 in each group, * P<0.05, Student’s t-test). Error bars represent SEM. (APPSwe/PS1L166P SE, APPSwe/PS1L166P mice housed in Standard Environment; APPSwe/PS1L166P EE, APPSwe/PS1L166P mice housed in Enriched Environment).
Mentions: Most notably EE completely reverted the spatial memory deficit displayed by 6-month-old APPSwe/PS1L166P mice reared in SE (Fig. 7). In fact, after 6 months spent in EE, APPSwe/PS1L166P mice significantly improved their performance (Two-way Repeated-Measures ANOVA, housing condition effect, P<0.05; day effect, P<0.001). The post-hoc test revealed that, since the second day of training, APPSwe/PS1L166P mice reared in EE spent significantly less time to reach the submerged platform relative to those which lived in SE (escape latency for APPSwe/PS1L166P mice 65.08±4.54 s in SE, 39.95±7.51 s in EE; Bonferroni, P<0.05). The memory deficit reversal in 6-month-old APPSwe/PS1L166P mice reared in EE was confirmed by a significant improvement in AR relative to SE mice, with an increase from the chance level of about 1 to a value greater than 3 (Fig. 7; Student’s t-test, P<0.05). On the contrary, in 2- and 4-month-old APPSwe/PS1L166P mice, the AR was higher than chance level in both SE and EE groups, without any significant difference between the two housing conditions (Fig. 7B, D; Student’s t-test, P>0.05). The effect of EE on the escape latency cannot be attributed to other factors like swimming velocity or distance covered, because these parameters showed significant differences neither between genotypes nor between caging conditions at any analyzed time point, suggesting equivalent vision, locomotor skills, and motivation (data not shown).

Bottom Line: On the other hand, chronic neuronal activity suppression by tetrodotoxin decreased the number of plaques without affecting intracellular amyloid.These results indicate that enriched environment exposure since early life has a protective effect on cognitive deterioration although transiently accelerates amyloid deposition.In addition, the effects of the enriched environment might be due to increased neuronal activity, because plaques were reduced by suppression of electrical signaling by tetrodotoxin.

View Article: PubMed Central - PubMed

Affiliation: Institute Cavalieri Ottolenghi (NICO), University of Torino, Orbassano (Torino), Italy.

ABSTRACT
Enriched environment exposure improves several aspects of cognitive performance in Alzheimer's disease patients and in animal models and, although the role of amyloid plaques is questionable, several studies also assessed their response to enriched environment, with contrasting results. Here we report that rearing APP(Swe)/PS1(L166P) mice in an enriched environment since birth rescued the spatial memory impairment otherwise present at 6 months of age. At the same time, the exposure to the enriched environment caused a transient acceleration of plaque formation, while there was no effect on intracellular staining with the 6E10 antibody, which recognizes β-amyloid, full length amyloid precursor protein and its C-terminal fragments. The anticipation of plaque formation required exposure during early development, suggesting an action within critical periods for circuits formation. On the other hand, chronic neuronal activity suppression by tetrodotoxin decreased the number of plaques without affecting intracellular amyloid. These results indicate that enriched environment exposure since early life has a protective effect on cognitive deterioration although transiently accelerates amyloid deposition. In addition, the effects of the enriched environment might be due to increased neuronal activity, because plaques were reduced by suppression of electrical signaling by tetrodotoxin.

Show MeSH
Related in: MedlinePlus