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Napoletani G, Vigli D, Cosentino L, et al. Stimulation of the Serotonin Receptor 7 Restores Brain Histone H3 Acetylation and MeCP2 Corepressor Protein Levels in a Female Mouse Model of Rett Syndrome. J Neuropathol Exp Neurol. 2021;80(3):265-273doi: 10.1093/jnen/nlaa158.
Napoletani, G., Vigli, D., Cosentino, L., Grieco, M., Talamo, M. C., Lacivita, E., Leopoldo, M., Laviola, G., Fuso, A., d'Erme, M., & De Filippis, B. (2021). Stimulation of the Serotonin Receptor 7 Restores Brain Histone H3 Acetylation and MeCP2 Corepressor Protein Levels in a Female Mouse Model of Rett Syndrome. Journal of neuropathology and experimental neurology, 80(3), 265-273. https://doi.org/10.1093/jnen/nlaa158
Napoletani, Giorgia, et al. "Stimulation of the Serotonin Receptor 7 Restores Brain Histone H3 Acetylation and MeCP2 Corepressor Protein Levels in a Female Mouse Model of Rett Syndrome." Journal of neuropathology and experimental neurology vol. 80,3 (2021): 265-273. doi: https://doi.org/10.1093/jnen/nlaa158
Napoletani G, Vigli D, Cosentino L, Grieco M, Talamo MC, Lacivita E, Leopoldo M, Laviola G, Fuso A, d'Erme M, De Filippis B. Stimulation of the Serotonin Receptor 7 Restores Brain Histone H3 Acetylation and MeCP2 Corepressor Protein Levels in a Female Mouse Model of Rett Syndrome. J Neuropathol Exp Neurol. 2021 Feb 22;80(3):265-273. doi: 10.1093/jnen/nlaa158. PMID: 33598674.
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J Neuropathol Exp Neurol. 2021 Feb 22;80(3):265-273. doi: 10.1093/jnen/nlaa158.

Stimulation of the Serotonin Receptor 7 Restores Brain Histone H3 Acetylation and MeCP2 Corepressor Protein Levels in a Female Mouse Model of Rett Syndrome.

Journal of neuropathology and experimental neurology

Giorgia Napoletani, Daniele Vigli, Livia Cosentino, Maddalena Grieco, Maria Cristina Talamo, Enza Lacivita, Marcello Leopoldo, Giovanni Laviola, Andrea Fuso, Maria d'Erme, Bianca De Filippis

Affiliations

  1. From the Department of Biochemical Sciences, Sapienza University of Roma, Roma, Italy.
  2. Center for Behavioral Sciences and Mental Health, Istituto Superiore di Sanità, Roma, Italy.
  3. Department of Pharmacy, University of Bari "Aldo Moro", Bari, Italy.
  4. Department of Experimental Medicine, Sapienza University of Roma, Roma, Italy.

PMID: 33598674 DOI: 10.1093/jnen/nlaa158

Abstract

Rett syndrome (RTT) is a rare neurological disorder caused by mutations in the X-linked MECP2 gene, 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 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.

© 2021 American Association of Neuropathologists, Inc. All rights reserved.

Keywords: Brain plasticity; Corepressor complexes; Histone acetylation; MeCP2; Rett syndrome; Serotonin receptor 7

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