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Título: | Abnormal mGluR-mediated synaptic plasticity and autism-like behaviours in Gprasp2 mutant mice | Autor: | Edfawy, Mohamed Guedes, Joana R. Pereira, Marta I. Laranjo, Mariana Carvalho, Mário J. Gao, Xian Ferreira, Pedro A. Caldeira, Gladys Franco, Lara O. Wang, Dongqing Cardoso, Ana Luísa Feng, Guoping Carvalho, Ana Luisa Peça, João |
Data: | 29-Mar-2019 | Editora: | Springer Nature | Projeto: | This research was supported by the Portuguese Foundation for Science and Technology (FCT) Investigator Programme IF/00812/2012, FCT grant POCI-01-0145-FEDER- 016682, Marie Curie Career Integration Grant (618525), NARSAD Young Investigator Grant from the Brain & Behaviour Research Foundation (#20733) and Bial Foundation Grant (266/2016) to J.P. We thank the support from FEDER/COMPETE institutional funds POCI-01-0145-FEDER-007440, BrainHealth 2020 CENTRO-01-0145-FEDER- 000008; fellowships SFRH/BD/51958/2012 (FCT PDBEB to M.E), SFRH/BPD/120611/ 2016 (FCT to J.R.G.), SFRH/BD/105878/2014 (FCT MIT-Portugal to M.J.C.) and NIMH grant R01MH097104 (to G.F.) | Título da revista, periódico, livro ou evento: | Nature Communications | Volume: | 10 | Número: | 1 | Resumo: | Autism spectrum disorder (ASD) is characterized by dysfunction in social interactions, stereotypical behaviours and high co-morbidity with intellectual disability. A variety of syndromic and non-syndromic neurodevelopmental disorders have been connected to alterations in metabotropic glutamate receptor (mGluR) signalling. These receptors contribute to synaptic plasticity, spine maturation and circuit development. Here, we investigate the physiological role of Gprasp2, a gene linked to neurodevelopmental disabilities and involved in the postendocytic sorting of G-protein-coupled receptors. We show that Gprasp2 deletion leads to ASD-like behaviour in mice and alterations in synaptic communication. Manipulating the levels of Gprasp2 bidirectionally modulates the surface availability of mGluR5 and produces alterations in dendritic complexity, spine density and synaptic maturation. Loss of Gprasp2 leads to enhanced hippocampal long-term depression, consistent with facilitated mGluR-dependent activation. These findings demonstrate a role for Gprasp2 in glutamatergic synapses and suggest a possible mechanism by which this gene is linked to neurodevelopmental diseases. | URI: | https://hdl.handle.net/10316/107187 | ISSN: | 2041-1723 | DOI: | 10.1038/s41467-019-09382-9 | Direitos: | openAccess |
Aparece nas coleções: | I&D CNC - Artigos em Revistas Internacionais FCTUC Ciências da Vida - Artigos em Revistas Internacionais IIIUC - Artigos em Revistas Internacionais |
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Abnormal-mGluRmediated-synaptic-plasticity-and-autismlike-behaviours-in-Gprasp2-mutant-miceNature-Communications.pdf | 8.35 MB | Adobe PDF | Ver/Abrir |
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