In 1999, two researchers from the Baylor College of Medicine in the US, Huga Zoghbi and Ruthie Amir, discovered that mutations in the MECP2 gene, found on the X chromosome, caused Rett syndrome, the second most common form of severe intellectual disability in girls.

MECP2 codes for the MeCP2 protein, which binds to methylated CpG dinucleotides and is essential for normal neuronal function. The gene was first identified by Scottish researcher Adrian Bird, and it is thought to be the cause of Rett syndrome in between 85 and 90 per cent of cases. A mutation in another gene, CDKL5, which is thought to have a role in the phosphorylation of MECP2, has been linked to the remaining cases.

That discovery was made by a group of Australian researchers, some of whom have now participated in a study of whether environmental enrichment helps ameliorate some of the symptoms of Rett syndrome, in particular a motor co-ordination deficit commonly seen in Rett girls.

The study, published in the European Journal of Neuroscience, found that environmental enrichment improves motor co-ordination in a mouse model of Rett, and also boosted levels of BDNF, the brain-derived neurotrophic factor that supports the survival of neurons and encourages new growth and differentiation, and which is thought to have a major role in neuronal development.

MeCP2 is primarily expressed in mature neurons and has a role in regulating the activity of specific targets, including BDNF. Last year, two studies looked at whether re-expression of MeCP2 in mice could reverse the symptoms of Rett. One, published in Science by Adrian Bird and Jacky Guy of the University of Edinburgh, found that restoration of a silenced gene saw a dramatic reversal in symptoms over a month.

The other, by Rudolph Jaenisch and Emanuala Giacometti from the Whitehead Institute at MIT, found a partial rescue of MeCP2 defiency by post-natal activation. Jaenisch’s team had earlier found that hyper-expression of BDNF dramatically reduced Rett symptoms in knockout mice.

According to the authors of the new Australian study, this earlier work provides compelling evidence suggesting that neurons are not irrevocably damaged by the absence of MeCP2 during development, and, furthermore, that amelioration of symptoms may be achieved by restoring normal neuronal functionality post-natally.

So the Australian team – involving PhD student Mari Kondo, Dr Laura Gray and Associate Professor Anthony Hannan from the Howard Florey Institute; Dr Gregory Pelka and Professor Patrick Tam from the Children’s Medical Research Institute (CMRI) in Sydney; and Professor John Christodoulou from the Children’s Hospital at Westmead – decided to test out whether environmental enrichment (EE), which has been shown beneficial effects on behaviourial phenotype as well as BDNF expression, may influence the disease outcome in a Rett mouse model.

They found that enrichment significantly improves motor co-ordination in female mutant mice– although not male mice, which usually die very young, as with boys with the mutation – and boosts levels of BDNF.

“Enrichment has already been shown to be very effective in other mouse models and other neurological diseases such as Huntington’s, Alzheimer’s and fragile X mental retardation,” Mari Kondo says. “So this is another one to add to the list of diseases where enrichment has a positive effect.”