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The stimulation of serotonin receptor 7 (5-HT7R) with its selective agonist LP-211 (0.25\u2009mg\/kg\/day for 7\u2009days) was proved to rescue neurobehavioral alterations in a mouse model of RTT. In the present study, we aimed at gaining insight into the mechanisms underpinning the efficacy of 5-HT7R pharmacological stimulation by investigating its epigenetic outcomes in the brain of RTT female mice bearing a truncating MeCP2 mutation. Treatment with LP-211 normalized the reduced histone H3 acetylation and HDAC3\/NCoR levels, and increased HDAC1\/Sin3a expression in RTT mouse cortex. Repeated 5-HT7R stimulation also appeared to strengthen the association between NCoR and MeCP2 in the same brain region. A different profile was found in RTT hippocampus, where LP-211 rescued H3 hyperacetylation and increased HDAC3 levels. Overall, the present data highlight a new scenario on the relationship between histone acetylation and serotoninergic pathways. 5-HT7R is confirmed as a pivotal therapeutic target for the recovery of neuronal function supporting the translational value of this promising pharmacological approach for RTT.<\/jats:p>","DOI":"10.1093\/jnen\/nlaa158","type":"journal-article","created":{"date-parts":[[2021,2,20]],"date-time":"2021-02-20T23:43:06Z","timestamp":1613864586000},"page":"265-273","source":"Crossref","is-referenced-by-count":9,"title":["Stimulation of the Serotonin Receptor 7 Restores Brain Histone H3 Acetylation and MeCP2 Corepressor Protein Levels in a Female Mouse Model of Rett Syndrome"],"prefix":"10.1093","volume":"80","author":[{"given":"Giorgia","family":"Napoletani","sequence":"first","affiliation":[{"name":"From the Department of Biochemical Sciences, Sapienza University of Roma , Roma, 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