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dc.contributor.author
Metzger, Michael W.
dc.contributor.author
Walser, Sandra M.
dc.contributor.author
Dedic, Nina
dc.contributor.author
Aprile García, Fernando
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Jakubcakova, Vladimira
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Adamczyk, Marek
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Webb, Katharine J.
dc.contributor.author
Uhr, Manfred
dc.contributor.author
Refojo, Damian
dc.contributor.author
Schmidt, Mathias V.
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Friess, Elisabeth
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Steiger, Axel
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Kimura, Mayumi
dc.contributor.author
Chen, Alon
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Holsboer, Florian
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Arzt, Eduardo Simon
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Wurst, Wolfgang
dc.contributor.author
Deussing, Jan M.
dc.date.available
2018-08-13T19:27:13Z
dc.date.issued
2017-11
dc.identifier.citation
Metzger, Michael W.; Walser, Sandra M.; Dedic, Nina; Aprile García, Fernando; Jakubcakova, Vladimira; et al.; Heterozygosity for the Mood Disorder-Associated Variant Gln460Arg Alters P2X7 Receptor Function and Sleep Quality; Society for Neuroscience; Journal of Neuroscience; 37; 48; 11-2017; 11688-11700
dc.identifier.issn
0270-6474
dc.identifier.uri
http://hdl.handle.net/11336/55204
dc.description.abstract
A single nucleotide polymorphism substitution from glutamine (Gln, Q) to arginine (Arg, R) at codon 460 of the purinergic P2X7 receptor (P2X7R) has repeatedly been associated with mood disorders. The P2X7R-Gln460Arg variant per se is not compromised in its function. However, heterologous expression of P2X7R-Gln460Arg together with wild-type P2X7R has recently been demonstrated to impair receptor function. Here we show that this also applies to humanized mice coexpressing both human P2X7R variants. Primary hippocampal cells derived from heterozygous mice showed an attenuated calcium uptake upon agonist stimulation. While humanized mice were unaffected in their behavioral repertoire under basal housing conditions, mice that harbor both P2X7R variants showed alterations in their sleep quality resembling signs of a prodromal disease stage. Also healthy heterozygous human subjects showed mild changes in sleep parameters. These results indicate that heterozygosity for the wild-type P2X7R and its mood disorder-associated variant P2X7R-Gln460Arg represents a genetic risk factor, which is potentially able to convey susceptibility to mood disorders.
dc.format
application/pdf
dc.language.iso
eng
dc.publisher
Society for Neuroscience
dc.rights
info:eu-repo/semantics/openAccess
dc.rights.uri
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.subject
Humanized Mouse Model
dc.subject
Mood Disorder
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P2x7 Receptor
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Purinergic Signaling
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Sleep
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Stress
dc.subject.classification
Inmunología
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Medicina Básica
dc.subject.classification
CIENCIAS MÉDICAS Y DE LA SALUD
dc.title
Heterozygosity for the Mood Disorder-Associated Variant Gln460Arg Alters P2X7 Receptor Function and Sleep Quality
dc.type
info:eu-repo/semantics/article
dc.type
info:ar-repo/semantics/artículo
dc.type
info:eu-repo/semantics/publishedVersion
dc.date.updated
2018-06-19T16:00:50Z
dc.journal.volume
37
dc.journal.number
48
dc.journal.pagination
11688-11700
dc.journal.pais
Estados Unidos
dc.journal.ciudad
Washington
dc.description.fil
Fil: Metzger, Michael W.. Max Planck Institut Fur Psychiatrie; Alemania
dc.description.fil
Fil: Walser, Sandra M.. Max Planck Institut Fur Psychiatrie; Alemania
dc.description.fil
Fil: Dedic, Nina. Max Planck Institut Fur Psychiatrie; Alemania
dc.description.fil
Fil: Aprile García, Fernando. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigación en Biomedicina de Buenos Aires - Instituto Partner de la Sociedad Max Planck; Argentina
dc.description.fil
Fil: Jakubcakova, Vladimira. Max Planck Institut Fur Psychiatrie; Alemania
dc.description.fil
Fil: Adamczyk, Marek. Max Planck Institut Fur Psychiatrie; Alemania
dc.description.fil
Fil: Webb, Katharine J.. Max Planck Institut Fur Psychiatrie; Alemania
dc.description.fil
Fil: Uhr, Manfred. Max Planck Institut Fur Psychiatrie; Alemania
dc.description.fil
Fil: Refojo, Damian. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigación en Biomedicina de Buenos Aires - Instituto Partner de la Sociedad Max Planck; Argentina
dc.description.fil
Fil: Schmidt, Mathias V.. Max Planck Institut Fur Psychiatrie; Alemania
dc.description.fil
Fil: Friess, Elisabeth. Max Planck Institut Fur Psychiatrie; Alemania
dc.description.fil
Fil: Steiger, Axel. Max Planck Institut Fur Psychiatrie; Alemania
dc.description.fil
Fil: Kimura, Mayumi. Max Planck Institut Fur Psychiatrie; Alemania
dc.description.fil
Fil: Chen, Alon. Max Planck Institut Fur Psychiatrie; Alemania. Weizmann Institute of Science; Israel
dc.description.fil
Fil: Holsboer, Florian. Max Planck Institut Fur Psychiatrie; Alemania
dc.description.fil
Fil: Arzt, Eduardo Simon. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigación en Biomedicina de Buenos Aires - Instituto Partner de la Sociedad Max Planck; Argentina
dc.description.fil
Fil: Wurst, Wolfgang. Institute of Developmental Genetics; Alemania. Technische Universität München-Weihenstephan; Alemania. German Center for Neurodegenerative Diseases; Alemania. Universität München; Alemania
dc.description.fil
Fil: Deussing, Jan M.. Max Planck Institut Fur Psychiatrie; Alemania
dc.journal.title
Journal of Neuroscience
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/doi/https://dx.doi.org/10.1523/JNEUROSCI.3487-16.2017
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/http://www.jneurosci.org/content/37/48/11688


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