Loss of Cntnap2 Causes Axonal Excitability Deficits, Developmental Delay in Cortical Myelination, and Abnormal Stereotyped Motor Behavior
| Autor: | Elior Peles, Martien J H Kas, Ricardo Scott, Hilgo Bruining, Lynette Lim, Nathalie Dehorter, Oscar Marín, Giorgia Bartolini, Sung Eun Bae, Kim C M van der Elst, Alberto Sanchez-Aguilera |
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| Přispěvatelé: | Israel Science Foundation, Ministerio de Economía y Competitividad (España), European Research Council, European Commission, Autism Speaks, Wellcome Trust, Kas lab |
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
Male
CNTNAP2 Developmental Disabilities Cognitive Neuroscience Mutant Action Potentials Stereotypic Movement Disorder Mice Transgenic Nerve Tissue Proteins Biology medicine.disease_cause Nerve Fibers Myelinated Synaptic Transmission 050105 experimental psychology Corpus Callosum White matter 03 medical and health sciences Myelin Mice Cellular and Molecular Neuroscience 0302 clinical medicine Postsynaptic potential medicine Journal Article Animals 0501 psychology and cognitive sciences Expressivity (genetics) Caspr2 Cerebral Cortex Mutation 05 social sciences Membrane Proteins Kv1-family potassium channels Axons 3. Good health Mice Inbred C57BL GABAergic interneurons axonal action potentials myelin medicine.anatomical_structure nervous system Excitatory postsynaptic potential Neuroscience 030217 neurology & neurosurgery |
| Zdroj: | Cerebral Cortex, 29(2), 586. Oxford University Press Scott, R, Sanchez Aguilera, A, van Elst, K, Lim, L, Dehorter, N, Bae, S E, Bartolini, G, Peles, E, Kas, M J H, Bruining, H & Marin, O 2017, ' Loss of Cntnap2 causes axonal excitability deficits, developmental delay in cortical myelination, and abnormal stereotyped motor behaviour ', Cerebral Cortex, vol. 29, no. 2, pp. 586-597 . https://doi.org/10.1093/cercor/bhx341 Digital.CSIC. Repositorio Institucional del CSIC instname Cerebral Cortex, 29(2). Oxford University Press |
| ISSN: | 1047-3211 |
| DOI: | 10.1093/cercor/bhx341 |
| Popis: | Contactin-associated protein-like 2 (Caspr2) is found at the nodes of Ranvier and has been associated with physiological properties of white matter conductivity. Genetic variation in CNTNAP2, the gene encoding Caspr2, has been linked to several neurodevelopmental conditions, yet pathophysiological effects of CNTNAP2 mutations on axonal physiology and brain myelination are unknown. Here, we have investigated mouse mutants for Cntnap2 and found profound deficiencies in the clustering of Kv1-family potassium channels in the juxtaparanodes of brain myelinated axons. These deficits are associated with a change in the waveform of axonal action potentials and increases in postsynaptic excitatory responses. We also observed that the normal process of myelination is delayed in Cntnap2 mutant mice. This later phenotype is a likely modulator of the developmental expressivity of the stereotyped motor behaviors that characterize Cntnap2 mutant mice. Altogether, our results reveal a mechanism linked to white matter conductivity through which mutation of CNTNAP2 may affect neurodevelopmental outcomes. This work was supported by grants from the Spanish Ministerio de Economía y Competitividad (SAF2010-20604) to R.S.; Israel Science Foundation to E.P.; Simons Foundation (SFARI 239766) to E.P. and O.M.; European Research Council (ERC-2011-AdG 293683) to O.M.; and European Autism Interventions – A Multicentre Study for Developing New Medications (EU-AIMS) to M.K. EU-AIMS is a project receiving support from the Innovative Medicines Initiative Joint Undertaking under grant agreement no. 115 300, resources of which are composed of financial contribution from the European Union’s Seventh Framework Programme (FP7/2007-2013), from the EFPIA companies in kind contribution, and from Autism Speaks. O.M. is a Wellcome Trust Investigator. |
| Databáze: | OpenAIRE |
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