| Autor: |
Napoletani, Giorgia, Vigli, Daniele, Cosentino, Livia, Grieco, Maddalena, Talamo, Maria Cristina, Lacivita, Enza, Leopoldo, Marcello, Laviola, Giovanni, Fuso, Andrea, d’Erme, Maria, De Filippis, Bianca |
| Zdroj: |
Journal of Neuropathology and Experimental Neurology; March 2021, Vol. 80 Issue: 3 p265-273, 9p |
| Abstrakt: |
Rett syndrome (RTT) is a rare neurological disorder caused by mutations in the X-linked MECP2gene, characterized by severe behavioral and physiological impairments for which no cure is available. The stimulation of serotonin receptor 7 (5-HT7R) with its selective agonist LP-211 (0.25 mg/kg/day for 7 days) 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 MeCP2mutation. 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. |
| Databáze: |
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