Global Impairment of Immediate-Early Genes Expression in Rett Syndrome Models and Patients Linked to Myelination Defects
Petazzi, Paolo (Instituto de Salud Carlos III)
Jorge-Torres, Olga Caridad (Institut Germans Trias i Pujol. Institut de Recerca contra la Leucèmia Josep Carreras)
Gómez Moruno, Antonio (Universitat de Vic - Universitat Central de Catalunya)
Scognamiglio, Iolanda (Institut d'Investigació Biomèdica de Bellvitge)
Serra-Musach, Jordi (Institut d'Investigació Biomèdica de Bellvitge)
Merkel, Angelika (Institut Germans Trias i Pujol. Institut de Recerca contra la Leucèmia Josep Carreras)
Grases, Daniela (Institut Germans Trias i Pujol. Institut de Recerca contra la Leucèmia Josep Carreras)
Xiol, Clara (Hospital Sant Joan de Déu (Manresa))
O'Callaghan, Maria del Mar (Centro de Investigación Biomédica en Red de Enfermedades Raras)
Armstrong, Judith (Centro de Investigación Biomédica en Red de Enfermedades Raras)
Esteller, M (Institut Germans Trias i Pujol. Institut de Recerca contra la Leucèmia Josep Carreras)
Guil, Sonia (Institut Germans Trias i Pujol. Institut de Recerca contra la Leucèmia Josep Carreras)

Date:	2023
Abstract:	Rett syndrome (RTT) is a severe neurodevelopmental disease caused almost exclusively by mutations to the MeCP2 gene. This disease may be regarded as a synaptopathy, with impairments affecting synaptic plasticity, inhibitory and excitatory transmission and network excitability. The complete understanding of the mechanisms behind how the transcription factor MeCP2 so profoundly affects the mammalian brain are yet to be determined. What is known, is that MeCP2 involvement in activity-dependent expression programs is a critical link between this protein and proper neuronal activity, which allows the correct maturation of connections in the brain. By using RNA-sequencing analysis, we found several immediate-early genes (IEGs, key mediators of activity-dependent responses) directly bound by MeCP2 at the chromatin level and upregulated in the hippocampus and prefrontal cortex of the Mecp2-KO mouse. Quantification of the IEGs response to stimulus both in vivo and in vitro detected an aberrant expression pattern in MeCP2-deficient neurons. Furthermore, altered IEGs levels were found in RTT patient's peripheral blood and brain regions of post-mortem samples, correlating with impaired expression of downstream myelination-related genes. Altogether, these data indicate that proper IEGs expression is crucial for correct synaptic development and that MeCP2 has a key role in the regulation of IEGs.
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Subject:	Rett syndrome ; MeCP2 ; EGR2 ; IEGs ; Myelination
Published in:	International journal of molecular sciences, Vol. 24 Núm. 2 (january 2023) , ISSN 1422-0067

DOI: 10.3390/ijms24021453
PMID: 36674969

19 p, 2.4 MB

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Research literature > UAB research groups literature > Research Centres and Groups (research output) > Health sciences and biosciences > Institut d'Investigació en Ciencies de la Salut Germans Trias i Pujol (IGTP) > Josep Carreras Leukaemia Research Institute
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