Environmental enrichment ameliorates a motor coordination deficit in a mouse model of Rett syndrome –Mecp2 gene dosage effects and BDNF expression

@article{Kondo2008EnvironmentalEA,
  title={Environmental enrichment ameliorates a motor coordination deficit in a mouse model of Rett syndrome –Mecp2 gene dosage effects and BDNF expression},
  author={Mari A. Kondo and Laura Gray and Gregory J. Pelka and John Christodoulou and Patrick P. L. Tam and Anthony John Hannan},
  journal={European Journal of Neuroscience},
  year={2008},
  volume={27}
}
Rett syndrome, commonly associated with mutations of the methyl CpG‐binding protein 2 (MECP2) gene, is characterised by an apparently normal early postnatal development followed by deterioration of acquired cognitive and motor coordination skills in early childhood. To evaluate whether environmental factors may influence the disease outcome of Rett syndrome, we tested the effect of environmental enrichment from 4 weeks of age on the behavioural competence of mutant mice harboring a Mecp2 tm1Tam… 
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Early Environmental Enrichment Moderates the Behavioral and Synaptic Phenotype of MeCP2 Null Mice
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It is 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.
Early motor phenotype detection in a female mouse model of Rett syndrome is improved by cross‐fostering
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Findings indicate that female Mecp2tm1.1bird‐/+ mice recapitulate many of the motor aspects of RTT syndrome earlier than previously appreciated, and that rearing conditions may impact the phenotypic severity and improve the ability to detect genotype differences in female MECp2 mutant mice.
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Together, these data indicate that significant clinically relevant benefit can be achieved in a mouse model of RTT with a chronic intermittent, low-dose treatment paradigm targeting the neurotrophin receptor TrkB.
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TLDR
The findings show that sensorimotor enrichment may ameliorate the motor deficiencies seen in this RTT mouse model and suggest that enrichment might be a viable treatment method for enhancing motor skill performance in girls with RTT.
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TLDR
Despite circuit hypoactivity and weakened functional connectivity across L2/3 and L5a, the Mecp2-null circuit’s firing pattern evolved with improved performance over two weeks, and trained mice became less anxious and lived 20% longer than untrained mice.
Partial reversal of Rett Syndrome-like symptoms in MeCP2 mutant mice
TLDR
Systemic treatment of MeCP2 mutant mice with an active peptide fragment of Insulin-like Growth Factor 1 (IGF-1) extends the life span of the mice, improves locomotor function, ameliorates breathing patterns, and reduces irregularity in heart rate.
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TLDR
Behavioural interventions such as environmental enrichment can reduce the functional deficit in Rett syndrome, contributing to the evidence-base for management and further understanding of epigenetic mechanisms.
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TLDR
Evidence of precocious behavioral markers of RTT is provided and an early developmental window of opportunities on which potential therapies could be investigated is identified, highlighting the need for increased attention to the presymptomatic phase.
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References

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