Reference:
GGP05236
Abstract:
Rett syndrome is a major cause of mental retardation, second only to the incidence of Down syndrome, and occurs almost exclusively in females. This disease manifests itself after a period of apparently normal development and causes growth retardation, severe psychomotor and autistic-like behaviors . The majority of cases of Rett syndrome is caused by a mutation of the MECP2 gene, which encodes a protein that binds to DNA and regulates the expression of other genes, including that of BDNF, a major neurotrophins involved in the regulation of brain development . Although many different mutations of the MECP2 protein have been studied, both in humans and in animal models, the molecular defects underlying the disease are not known. In this research project, we will use a mouse model that carries a mutation in the MECP2 gene and reproducing the human Rett syndrome to study the molecular basis of the disease and to understand how it affects the neural circuits and brain function . In particular, we will analyze the inhibitory circuits and the expression of BDNF in the brains of mice carrying the mutation, to see if there are abnormalities that could explain the defects in the development, maturation and function of neural circuits . Moreover, we will evaluate the effect in the animal model of a behavioral therapy or the reestablishment of physiological levels of BDNF as a possible basis of future therapies in the patient. The knowledge of the molecular events resulting from the mutation of the MECP2 gene is a fundamental step for understanding the pathogenesis of Rett syndrome and the development of effective therapies for the treatment of this severe form of mental retardation.
PROJECT DETAILS
beginning: 2005.
end: 2008.
Country of research: Italy
Counry of funding source: Italy
Funding organization: Telethon
Financing: PRIVATE FUNDERS – 412 700 €