Altered neuronal network and rescue in a human MECP2 duplication model

Détails

ID Serval
serval:BIB_9E779F1B125B
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Altered neuronal network and rescue in a human MECP2 duplication model
Périodique
Mol Psychiatry
Auteur⸱e⸱s
Nageshappa S., Carromeu C., Trujillo C. A., Mesci P., Espuny-Camacho I., Pasciuto E., Vanderhaeghen P., Verfaillie C. M., Raitano S., Kumar A., Carvalho C. M., Bagni C., Ramocki M. B., Araujo B. H., Torres L. B., Lupski J. R., Van Esch H., Muotri A. R.
ISSN
1476-5578 (Electronic)
ISSN-L
1359-4184
Statut éditorial
Publié
Date de publication
02/2016
Volume
21
Numéro
2
Pages
178-88
Notes
Nageshappa, S
Carromeu, C
Trujillo, C A
Mesci, P
Espuny-Camacho, I
Pasciuto, E
Vanderhaeghen, P
Verfaillie, C M
Raitano, S
Kumar, A
Carvalho, C M B
Bagni, C
Ramocki, M B
Araujo, B H S
Torres, L B
Lupski, J R
Van Esch, H
Muotri, A R
eng
1-DP2-OD006495-01/OD/NIH HHS/
DP2 OD006495/OD/NIH HHS/
R01NS058529/NS/NINDS NIH HHS/
K08 NS062711/NS/NINDS NIH HHS/
R01 MH094753/MH/NIMH NIH HHS/
R01 NS058529/NS/NINDS NIH HHS/
R01MH094753/MH/NIMH NIH HHS/
Comparative Study
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
England
2015/09/09 06:00
Mol Psychiatry. 2016 Feb;21(2):178-88. doi: 10.1038/mp.2015.128. Epub 2015 Sep 8.
Résumé
Increased 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.
Mots-clé
Cell Differentiation, Dendrites/metabolism, Gene Dosage/physiology, Gene Duplication/genetics, Genetic Association Studies, Humans, Induced Pluripotent Stem Cells, Male, Methyl-CpG-Binding Protein 2/*genetics/*physiology, Nerve Net/*metabolism, Neurogenesis, Neurons
Pubmed
Création de la notice
06/03/2017 17:23
Dernière modification de la notice
20/08/2019 15:04
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