Altered neuronal network and rescue in a human MECP2 duplication model

dc.creatorNageshappa, Savitha
dc.creatorCarromeu, Cassiano
dc.creatorTrujillo, Cleber A.
dc.creatorMesci, Pinar
dc.creatorEspuny-Camacho, Ira
dc.creatorPasciuto, Emanuela
dc.creatorVanderhaeghen, Pierre
dc.creatorVerfaillie, Catherine
dc.creatorRaitano, Susanna
dc.creatorKumar, Anujith
dc.creatorCarvalho, Claudia Márcia Benedetto de
dc.creatorBagni, Claudia
dc.creatorRamocki, Melissa B.
dc.creatorAraujo, Bruno H. S.
dc.creatorTorres, Laila B.
dc.creatorLupski, James R.
dc.creatorEsch, Hilde Van
dc.creatorMuotri, Alysson R.
dc.date2016-07-13T18:45:47Z
dc.date2016-07-13T18:45:47Z
dc.date2016
dc.date.accessioned2023-09-26T23:50:08Z
dc.date.available2023-09-26T23:50:08Z
dc.identifierNAGESHAPPA, Savitha et al. Altered neuronal network and rescue in a human MECP2 duplication model. Mol Psychiatry., vol. 21, n. 2, p. 178-88, 2016.
dc.identifier1359-4184
dc.identifierhttps://www.arca.fiocruz.br/handle/icict/14854
dc.identifier10.1038/mp.2015.128
dc.identifier.urihttps://repositorioslatinoamericanos.uchile.cl/handle/2250/8894730
dc.descriptionIncreased dosage of methyl-CpG-binding protein-2 (MeCP2) results in a dramatic neurodevelopmental phenotype with onset at birth. We generated induced pluripotent stem cells (iPSCs) from patients with the MECP2 duplication syndrome (MECP2dup), carrying different duplication sizes, to study the impact of increased MeCP2 dosage in human neurons. We show that cortical neurons derived from these different MECP2dup iPSC lines have increased synaptogenesis and dendritic complexity. In addition, using multi-electrodes arrays, we show that neuronal network synchronization was altered in MECP2dup-derived neurons. Given MeCP2 functions at the epigenetic level, we tested whether these alterations were reversible using a library of compounds with defined activity on epigenetic pathways. One histone deacetylase inhibitor, NCH-51, was validated as a potential clinical candidate. Interestingly, this compound has never been considered before as a therapeutic alternative for neurological disorders. Our model recapitulates early stages of the human MECP2 duplication syndrome and represents a promising cellular tool to facilitate therapeutic drug screening for severe neurodevelopmental disorders.
dc.formatapplication/pdf
dc.languageeng
dc.publisherNature Publishing Group Specialist Journals
dc.rightsopen access
dc.subjectMeCP2
dc.subjectduplication syndrome
dc.subjectinduced pluripotent stem cells
dc.subjectdisease modeling
dc.subjectepigenetic drugs
dc.subjectHDAC inhibitors
dc.subjectNCH-51
dc.subjectdrug screening
dc.subjectmulti-electrode arrays
dc.titleAltered neuronal network and rescue in a human MECP2 duplication model
dc.typeArticle


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