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A centronuclear myopathy-causing mutation in dynamin-2 disrupts neuronal morphology and excitatory synaptic transmission in a murine model of the disease

dc.contributor.authorArriagada-Diaz, Jorge
dc.contributor.authorFlores-Muñoz, Carolina
dc.contributor.authorGomez-Soto, Bárbara
dc.contributor.authorLabraña-Allende, Marjorie
dc.contributor.authorMattar-Araos, Michelle
dc.contributor.authorPrado-Vega, Lorena
dc.contributor.authorHinostroza, Fernando
dc.contributor.authorGajardo, Ivana
dc.contributor.authorGuerra-Fernández, María José
dc.contributor.authorBevilacqua, Jorge A.
dc.contributor.authorCárdenas, Ana M.
dc.contributor.authorBitoun, Marc
dc.contributor.authorArdiles, Alvaro O.
dc.contributor.authorGonzalez-Jamett, Arlek M.
dc.date.accessioned2024-12-27T14:03:46Z
dc.date.available2024-12-27T14:03:46Z
dc.date.issued2023
dc.identifier.urihttp://repositorio.ucm.cl/handle/ucm/5818
dc.description.abstractAims Dynamin-2 is a large GTPase, a member of the dynamin superfamily that regulates membrane remodelling and cytoskeleton dynamics. Mutations in the dynamin-2 gene (DNM2) cause autosomal dominant centronuclear myopathy (CNM), a congenital neuromuscular disorder characterised by progressive weakness and atrophy of the skeletal muscles. Cognitive defects have been reported in some DNM2-linked CNM patients suggesting that these mutations can also affect the central nervous system (CNS). Here we studied how a dynamin-2 CNM-causing mutation influences the CNS function. Methods Heterozygous mice harbouring the p.R465W mutation in the dynamin–2 gene (HTZ), the most common causing autosomal dominant CNM, were used as disease model. We evaluated dendritic arborisation and spine density in hippocampal cultured neurons, analysed excitatory synaptic transmission by electrophysiological field recordings in hippocampal slices, and evaluated cognitive function by performing behavioural tests. Results HTZ hippocampal neurons exhibited reduced dendritic arborisation and lower spine density than WT neurons, which was reversed by transfecting an interference RNA against the dynamin-2 mutant allele. Additionally, HTZ mice showed defective hippocampal excitatory synaptic transmission and reduced recognition memory compared to the WT condition. Conclusion Our findings suggest that the dynamin-2 p.R465W mutation perturbs the synaptic and cognitive function in a CNM mouse model and support the idea that this GTPase plays a key role in regulating neuronal morphology and excitatory synaptic transmission in the hippocampus.es_CL
dc.language.isoenes_CL
dc.rightsAtribución-NoComercial-SinDerivadas 3.0 Chile*
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/3.0/cl/*
dc.sourceNeuropathology and Applied Neurobiology, 49(4), e12918es_CL
dc.subjectCentronuclear myopathyes_CL
dc.subjectDendritic arborisationes_CL
dc.subjectDendritic spineses_CL
dc.subjectDynamin-2es_CL
dc.subjectNeuronal morphologyes_CL
dc.subjectSynaptic transmissiones_CL
dc.titleA centronuclear myopathy-causing mutation in dynamin-2 disrupts neuronal morphology and excitatory synaptic transmission in a murine model of the diseasees_CL
dc.typeArticlees_CL
dc.ucm.facultadFacultad de Medicinaes_CL
dc.ucm.indexacionScopuses_CL
dc.ucm.indexacionIsies_CL
dc.ucm.uriwiley.ucm.elogim.com/doi/10.1111/nan.12918es_CL
dc.ucm.doidoi.org/10.1111/nan.12918es_CL


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