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Artículo

Heterozygosity for the Mood Disorder-Associated Variant Gln460Arg Alters P2X7 Receptor Function and Sleep Quality

Metzger, Michael W.; Walser, Sandra M.; Dedic, Nina; Aprile García, FernandoIcon ; Jakubcakova, Vladimira; Adamczyk, Marek; Webb, Katharine J.; Uhr, Manfred; Refojo, DamianIcon ; Schmidt, Mathias V.; Friess, Elisabeth; Steiger, Axel; Kimura, Mayumi; Chen, Alon; Holsboer, Florian; Arzt, Eduardo SimonIcon ; Wurst, Wolfgang; Deussing, Jan M.
Fecha de publicación: 11/2017
Editorial: Society for Neuroscience
Revista: Journal of Neuroscience
ISSN: 0270-6474
Idioma: Inglés
Tipo de recurso: Artículo publicado
Clasificación temática:
Inmunología

Resumen

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.
Palabras clave: Humanized Mouse Model , Mood Disorder , P2x7 Receptor , Purinergic Signaling , Sleep , Stress
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info:eu-repo/semantics/openAccess Excepto donde se diga explícitamente, este item se publica bajo la siguiente descripción: Creative Commons Attribution-NonCommercial-ShareAlike 2.5 Unported (CC BY-NC-SA 2.5)
Identificadores
URI: http://hdl.handle.net/11336/55204
DOI: https://dx.doi.org/10.1523/JNEUROSCI.3487-16.2017
URL: http://www.jneurosci.org/content/37/48/11688
Colecciones
Articulos(IBIOBA - MPSP)
Articulos de INST. D/INV.EN BIOMED.DE BS AS-CONICET-INST. PARTNER SOCIEDAD MAX PLANCK
Citación
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
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