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Unconventional transcriptional response to environmental enrichment in a mouse model of Rett syndrome.

Kerr B, Silva PA, Walz K, Young JI - PLoS ONE (2010)

Bottom Line: RTT is characterized by psychomotor retardation, purposeless hand movements, autistic-like behavior and abnormal gait.We found that EE delayed and attenuated some neurological alterations presented by Mecp2(-/y) mice and prevented the development of motor discoordination and anxiety-related abnormalities.We found that EE induced downregulation of several synaptic markers, suggesting that the partial prevention of RTT-associated phenotypes is achieved through a non-conventional transcriptional program.

View Article: PubMed Central - PubMed

Affiliation: Department of Biology, Centro de Estudios Científicos, Valdivia, Chile.

ABSTRACT

Background: Rett syndrome (RTT) is an X-linked postnatal neurodevelopmental disorder caused by mutations in the gene encoding methyl-CpG binding protein 2 (MeCP2) and one of the leading causes of mental retardation in females. RTT is characterized by psychomotor retardation, purposeless hand movements, autistic-like behavior and abnormal gait. We studied the effects of environmental enrichment (EE) on the phenotypic manifestations of a RTT mouse model that lacks MeCP2 (Mecp2(-/y)).

Principal findings: We found that EE delayed and attenuated some neurological alterations presented by Mecp2(-/y) mice and prevented the development of motor discoordination and anxiety-related abnormalities. To define the molecular correlate of this beneficial effect of EE, we analyzed the expression of several synaptic marker genes whose expression is increased by EE in several mouse models.

Conclusions/significance: We found that EE induced downregulation of several synaptic markers, suggesting that the partial prevention of RTT-associated phenotypes is achieved through a non-conventional transcriptional program.

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Related in: MedlinePlus

Environmental Enrichment does not modify life span or body weight of Mecp2−/y mice.A, Kaplan-Meier plots showing the survival of Mecp2−/y-SC (open circles) and Mecp2−/y-EE (closed circles) since the initiation of the enrichment period. B, Growth curves of mice showed in A. The body weights of Mecp2−/y mice, irrespective of housing conditions, dropped abruptly after 14 weeks and were therefore not included in the graph. Data represent mean ± SEM. The total number of animals in each group is shown (n). No significant differences were found between Mecp2−/y-SC and Mecp2−/y-EE according to ANOVA tukey test.
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pone-0011534-g001: Environmental Enrichment does not modify life span or body weight of Mecp2−/y mice.A, Kaplan-Meier plots showing the survival of Mecp2−/y-SC (open circles) and Mecp2−/y-EE (closed circles) since the initiation of the enrichment period. B, Growth curves of mice showed in A. The body weights of Mecp2−/y mice, irrespective of housing conditions, dropped abruptly after 14 weeks and were therefore not included in the graph. Data represent mean ± SEM. The total number of animals in each group is shown (n). No significant differences were found between Mecp2−/y-SC and Mecp2−/y-EE according to ANOVA tukey test.

Mentions: Comparison of life span of Mecp2−/y mice subjected to environmental enrichment (Mecp2−/y-EE) or to standard conditions (Mecp2−/y-SC) showed that life expectancy (similar 0.5 probability survival rate, approximately 6 weeks) was not modified by EE (figure 1A).


Unconventional transcriptional response to environmental enrichment in a mouse model of Rett syndrome.

Kerr B, Silva PA, Walz K, Young JI - PLoS ONE (2010)

Environmental Enrichment does not modify life span or body weight of Mecp2−/y mice.A, Kaplan-Meier plots showing the survival of Mecp2−/y-SC (open circles) and Mecp2−/y-EE (closed circles) since the initiation of the enrichment period. B, Growth curves of mice showed in A. The body weights of Mecp2−/y mice, irrespective of housing conditions, dropped abruptly after 14 weeks and were therefore not included in the graph. Data represent mean ± SEM. The total number of animals in each group is shown (n). No significant differences were found between Mecp2−/y-SC and Mecp2−/y-EE according to ANOVA tukey test.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2902516&req=5

pone-0011534-g001: Environmental Enrichment does not modify life span or body weight of Mecp2−/y mice.A, Kaplan-Meier plots showing the survival of Mecp2−/y-SC (open circles) and Mecp2−/y-EE (closed circles) since the initiation of the enrichment period. B, Growth curves of mice showed in A. The body weights of Mecp2−/y mice, irrespective of housing conditions, dropped abruptly after 14 weeks and were therefore not included in the graph. Data represent mean ± SEM. The total number of animals in each group is shown (n). No significant differences were found between Mecp2−/y-SC and Mecp2−/y-EE according to ANOVA tukey test.
Mentions: Comparison of life span of Mecp2−/y mice subjected to environmental enrichment (Mecp2−/y-EE) or to standard conditions (Mecp2−/y-SC) showed that life expectancy (similar 0.5 probability survival rate, approximately 6 weeks) was not modified by EE (figure 1A).

Bottom Line: RTT is characterized by psychomotor retardation, purposeless hand movements, autistic-like behavior and abnormal gait.We found that EE delayed and attenuated some neurological alterations presented by Mecp2(-/y) mice and prevented the development of motor discoordination and anxiety-related abnormalities.We found that EE induced downregulation of several synaptic markers, suggesting that the partial prevention of RTT-associated phenotypes is achieved through a non-conventional transcriptional program.

View Article: PubMed Central - PubMed

Affiliation: Department of Biology, Centro de Estudios Científicos, Valdivia, Chile.

ABSTRACT

Background: Rett syndrome (RTT) is an X-linked postnatal neurodevelopmental disorder caused by mutations in the gene encoding methyl-CpG binding protein 2 (MeCP2) and one of the leading causes of mental retardation in females. RTT is characterized by psychomotor retardation, purposeless hand movements, autistic-like behavior and abnormal gait. We studied the effects of environmental enrichment (EE) on the phenotypic manifestations of a RTT mouse model that lacks MeCP2 (Mecp2(-/y)).

Principal findings: We found that EE delayed and attenuated some neurological alterations presented by Mecp2(-/y) mice and prevented the development of motor discoordination and anxiety-related abnormalities. To define the molecular correlate of this beneficial effect of EE, we analyzed the expression of several synaptic marker genes whose expression is increased by EE in several mouse models.

Conclusions/significance: We found that EE induced downregulation of several synaptic markers, suggesting that the partial prevention of RTT-associated phenotypes is achieved through a non-conventional transcriptional program.

Show MeSH
Related in: MedlinePlus