Rett syndrome (RTT) is a neurodevelopmental disorder caused by mutations in the X-linked MECP2 gene, characterized by motor dysfunction, respiratory abnormalities and cognitive deficits. To date, no cure is available. At the cellular level, RTT is characterized by morphological and functional synaptic defects which are in part attributed to non-cell autonomous mechanisms mainly mediated by astrocytes. We have demonstrated that Mecp2 knock-out astrocytes fail to sustain synaptogenesis in wild-type neurons, and this impairment is associated with an excessive release of interleukin 6 (IL-6). Notably, blocking IL-6 prevents synaptic alterations, suggesting the possibility to target this cytokine for therapeutic purposes. My study aims to extend in vitro findings moving to in vivo validation and exploring IL-6 as a therapeutic target in Mecp2 heterozygous (HET) mice. We thus analyzed IL-6 expression in the brain of HET animals along disease progression, finding an IL-6 increase in symptomatic mice. To establish whether IL-6 overexpression is limited to Mecp2- cells, we took advantage of the Mecp2/EGFP model. Further, we started testing whether IL-6 blockade restores synaptic integrity and improves neurological function in RTT animals. By clarifying IL-6's role in RTT and evaluating its therapeutic potential, this study could pave the way for novel treatments
