Synaptic plasticity and signaling in rett syndrome

Authors

  • Grazia Della Sala,

    1. Department of Neuroscience, Psychology, Drug Research and Child Health NEUROFARBA, University of Florence, Florence, Italy
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  • Tommaso Pizzorusso

    Corresponding author
    1. Department of Neuroscience, Psychology, Drug Research and Child Health NEUROFARBA, University of Florence, Florence, Italy
    2. Inst Neuroscience CNR, Pisa, Italy
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ABSTRACT

Rett syndrome (RTT) is a disorder that is caused in the majority of cases by mutations in the gene methyl-CpG-binding protein-2 (MeCP2). Children with RTT are generally characterized by normal development up to the first year and a half of age, after which they undergo a rapid regression marked by a deceleration of head growth, the onset of stereotyped hand movements, irregular breathing, and seizures. Animal models of RTT with good construct and face validity are available. Their analysis showed that homeostatic regulation of MeCP2 gene is necessary for normal CNS functioning and that multiple complex pathways involving different neuronal and glial cell types are disrupted in RTT models. However, it is increasingly clear that RTT pathogenetic mechanisms converge at synaptic level impairing synaptic transmission and plasticity. We review novel findings showing how specific synaptic mechanisms and related signaling pathways are affected in RTT models. © 2013 Wiley Periodicals, Inc. Develop Neurobiol 74: 178–196, 2014

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