The protein associated with Rett syndrome, is among a group of three proteins that affect the function of a gene previously linked to OCD.

‘Since the same gene is affected in both Rett syndrome and obsessive compulsive behaviors (OCD), the repetitive behavior in Rett syndrome can be stopped after reintroducing the gene into a particular brain region that is involved in OCD.’

Relatively little is known about the neuronal causes of Rett syndrome, but UT Southwestern Medical Center scientists have now identified a process in the brains of mice that might explain the repetitive actions that could be a key step in developing treatments to eliminate symptoms that drastically impair the quality of life in Rett patients.




“We are exploring the processes that contribute to Rett syndrome in an effort to develop treatments that may prove useful in the disease,” said Dr. Lisa Monteggia, Professor of Neuroscience with the O’Donnell Jr. Brain Institute, who led the research published in Nature Neuroscience.
The study demonstrated that MeCP2 , the protein which does not work properly in Rett syndrome, is among a group of three proteins that affect the function of a gene previously linked to obsessive compulsive disorder. Researchers were able to induce and then suppress repetitive behaviors in mice by changing the levels of these three proteins at the synapse – the communication junction between nerve cells.
The research is a significant advancement in the understanding of how dysfunction in MeCP2 leads to key symptoms associated with Rett syndrome. Although MeCP2 was identified less than two decades ago as the cause of the postnatal neurological disorder, the link between the protein’s dysfunction and the specific neurological symptoms characteristic of the disease remains elusive.
While current medications and behavioral therapy can sometimes diminish symptoms such as seizures and hand behaviors, no treatment exists to eradicate or reverse the disorder and the repetitive stereotyped behaviors, due to a lack of knowledge about how MeCP2 dysfunction gives rise to these and other symptoms.
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Dr. Monteggia’s team found that MeCP2 controls the function of a gene called SAPAP3, which has been linked to obsessive compulsive disorder in humans. Disrupting the interaction between MeCP2 and the target gene SAPAP3 caused mice to groom themselves excessively; this repetitive behavior stopped after researchers reintroduced SAPAP3 into a particular brain region that is involved in obsessive compulsive behaviors. The research group also identified that MeCP2 formed a complex with histone deacetylase proteins, HDAC1 and HDAC2, to regulate SAPAP3’s function.
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In addition to the Rett-related finding, Dr. Monteggia’s team found that the removal of both HDAC1 and HDAC2 from the brain can kill neurons. This outcome is notable because studies elsewhere had demonstrated the potential for treating memory loss by selectively inhibiting the HDAC2 protein.
Dr. Monteggia said this finding does not mean certain HDAC inhibitors can’t be effective, but the study does demonstrate that non-specific inhibitors and certain combinations may worsen the problem.
Source-Medindia