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Inhibitory neurons drive Rett Syndrome symptomsAdd to my bookmarks

Nature Neuroscience

April 29, 2014

The specific loss of function of the protein MeCP2 in inhibitory neurons in the forebrains of mice drives the onset of sensory deficits and seizures reported in Rett Syndrome, finds a paper published this week in Nature Neuroscience. This study provides important insight into the identity of the cells, which appear to mediate many of the debilitating symptoms associated with Rett Syndrome, and suggests that strategies aimed at replacing MeCP2 in these neurons might be a viable therapeutic approach.

Rett Syndrome is a neurodevelopmental disorder that is believed to result from mutations in the gene MeCP2. Symptoms of Rett Syndrome include small head and brain size, breathing abnormalities, intellectual disability, seizures and sensory (auditory and/or visual) deficits.

Zhaolan Zhou and colleagues report that deleting MeCP2 specifically in one class of neurons, the forebrain GABAergic inhibitory interneurons, in mice is sufficient to recapitulate the auditory disturbances and seizures that are associated with the disease. However, deleting the gene from another class of neurons, excitatory glutamatergic neurons, did not show this result. In addition, replacing ‘normal’ MeCP2 expression in the inhibitory neurons is sufficient to restore auditory processing and ameliorate seizures in these animals. It is not entirely clear why MeCP2 expression is necessary specifically in GABAergic inhibitory neurons or precisely how these neurons contribute to sensory deficits and seizure generation.

DOI:10.1038/nn.3710 | Original article

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