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

Autores
Metzger, Michael W.; Walser, Sandra M.; Dedic, Nina; Aprile García, Fernando; Jakubcakova, Vladimira; Adamczyk, Marek; Webb, Katharine J.; Uhr, Manfred; Refojo, Damian; Schmidt, Mathias V.; Friess, Elisabeth; Steiger, Axel; Kimura, Mayumi; Chen, Alon; Holsboer, Florian; Arzt, Eduardo Simon; Wurst, Wolfgang; Deussing, Jan M.
Año de publicación
2017
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
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.
Fil: Metzger, Michael W.. Max Planck Institut Fur Psychiatrie; Alemania
Fil: Walser, Sandra M.. Max Planck Institut Fur Psychiatrie; Alemania
Fil: Dedic, Nina. Max Planck Institut Fur Psychiatrie; Alemania
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
Fil: Jakubcakova, Vladimira. Max Planck Institut Fur Psychiatrie; Alemania
Fil: Adamczyk, Marek. Max Planck Institut Fur Psychiatrie; Alemania
Fil: Webb, Katharine J.. Max Planck Institut Fur Psychiatrie; Alemania
Fil: Uhr, Manfred. Max Planck Institut Fur Psychiatrie; Alemania
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
Fil: Schmidt, Mathias V.. Max Planck Institut Fur Psychiatrie; Alemania
Fil: Friess, Elisabeth. Max Planck Institut Fur Psychiatrie; Alemania
Fil: Steiger, Axel. Max Planck Institut Fur Psychiatrie; Alemania
Fil: Kimura, Mayumi. Max Planck Institut Fur Psychiatrie; Alemania
Fil: Chen, Alon. Max Planck Institut Fur Psychiatrie; Alemania. Weizmann Institute of Science; Israel
Fil: Holsboer, Florian. Max Planck Institut Fur Psychiatrie; Alemania
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
Fil: Wurst, Wolfgang. Institute of Developmental Genetics; Alemania. Technische Universität München-Weihenstephan; Alemania. German Center for Neurodegenerative Diseases; Alemania. Universität München; Alemania
Fil: Deussing, Jan M.. Max Planck Institut Fur Psychiatrie; Alemania
Materia
HUMANIZED MOUSE MODEL
MOOD DISORDER
P2X7 RECEPTOR
PURINERGIC SIGNALING
SLEEP
STRESS
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/55204
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/55204
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Heterozygosity for the Mood Disorder-Associated Variant Gln460Arg Alters P2X7 Receptor Function and Sleep QualityMetzger, Michael W.Walser, Sandra M.Dedic, NinaAprile García, FernandoJakubcakova, VladimiraAdamczyk, MarekWebb, Katharine J.Uhr, ManfredRefojo, DamianSchmidt, Mathias V.Friess, ElisabethSteiger, AxelKimura, MayumiChen, AlonHolsboer, FlorianArzt, Eduardo SimonWurst, WolfgangDeussing, Jan M.HUMANIZED MOUSE MODELMOOD DISORDERP2X7 RECEPTORPURINERGIC SIGNALINGSLEEPSTRESShttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3A 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.Fil: Metzger, Michael W.. Max Planck Institut Fur Psychiatrie; AlemaniaFil: Walser, Sandra M.. Max Planck Institut Fur Psychiatrie; AlemaniaFil: Dedic, Nina. Max Planck Institut Fur Psychiatrie; AlemaniaFil: 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; ArgentinaFil: Jakubcakova, Vladimira. Max Planck Institut Fur Psychiatrie; AlemaniaFil: Adamczyk, Marek. Max Planck Institut Fur Psychiatrie; AlemaniaFil: Webb, Katharine J.. Max Planck Institut Fur Psychiatrie; AlemaniaFil: Uhr, Manfred. Max Planck Institut Fur Psychiatrie; AlemaniaFil: 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; ArgentinaFil: Schmidt, Mathias V.. Max Planck Institut Fur Psychiatrie; AlemaniaFil: Friess, Elisabeth. Max Planck Institut Fur Psychiatrie; AlemaniaFil: Steiger, Axel. Max Planck Institut Fur Psychiatrie; AlemaniaFil: Kimura, Mayumi. Max Planck Institut Fur Psychiatrie; AlemaniaFil: Chen, Alon. Max Planck Institut Fur Psychiatrie; Alemania. Weizmann Institute of Science; IsraelFil: Holsboer, Florian. Max Planck Institut Fur Psychiatrie; AlemaniaFil: 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; ArgentinaFil: Wurst, Wolfgang. Institute of Developmental Genetics; Alemania. Technische Universität München-Weihenstephan; Alemania. German Center for Neurodegenerative Diseases; Alemania. Universität München; AlemaniaFil: Deussing, Jan M.. Max Planck Institut Fur Psychiatrie; AlemaniaSociety for Neuroscience2017-11info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/55204Metzger, 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; 11688-117000270-6474CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1523/JNEUROSCI.3487-16.2017info:eu-repo/semantics/altIdentifier/url/http://www.jneurosci.org/content/37/48/11688info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T10:29:44Zoai:ri.conicet.gov.ar:11336/55204instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-29 10:29:44.907CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Heterozygosity for the Mood Disorder-Associated Variant Gln460Arg Alters P2X7 Receptor Function and Sleep Quality
title Heterozygosity for the Mood Disorder-Associated Variant Gln460Arg Alters P2X7 Receptor Function and Sleep Quality
spellingShingle Heterozygosity for the Mood Disorder-Associated Variant Gln460Arg Alters P2X7 Receptor Function and Sleep Quality
Metzger, Michael W.
HUMANIZED MOUSE MODEL
MOOD DISORDER
P2X7 RECEPTOR
PURINERGIC SIGNALING
SLEEP
STRESS
title_short Heterozygosity for the Mood Disorder-Associated Variant Gln460Arg Alters P2X7 Receptor Function and Sleep Quality
title_full Heterozygosity for the Mood Disorder-Associated Variant Gln460Arg Alters P2X7 Receptor Function and Sleep Quality
title_fullStr Heterozygosity for the Mood Disorder-Associated Variant Gln460Arg Alters P2X7 Receptor Function and Sleep Quality
title_full_unstemmed Heterozygosity for the Mood Disorder-Associated Variant Gln460Arg Alters P2X7 Receptor Function and Sleep Quality
title_sort Heterozygosity for the Mood Disorder-Associated Variant Gln460Arg Alters P2X7 Receptor Function and Sleep Quality
dc.creator.none.fl_str_mv Metzger, Michael W.
Walser, Sandra M.
Dedic, Nina
Aprile García, Fernando
Jakubcakova, Vladimira
Adamczyk, Marek
Webb, Katharine J.
Uhr, Manfred
Refojo, Damian
Schmidt, Mathias V.
Friess, Elisabeth
Steiger, Axel
Kimura, Mayumi
Chen, Alon
Holsboer, Florian
Arzt, Eduardo Simon
Wurst, Wolfgang
Deussing, Jan M.
author Metzger, Michael W.
author_facet Metzger, Michael W.
Walser, Sandra M.
Dedic, Nina
Aprile García, Fernando
Jakubcakova, Vladimira
Adamczyk, Marek
Webb, Katharine J.
Uhr, Manfred
Refojo, Damian
Schmidt, Mathias V.
Friess, Elisabeth
Steiger, Axel
Kimura, Mayumi
Chen, Alon
Holsboer, Florian
Arzt, Eduardo Simon
Wurst, Wolfgang
Deussing, Jan M.
author_role author
author2 Walser, Sandra M.
Dedic, Nina
Aprile García, Fernando
Jakubcakova, Vladimira
Adamczyk, Marek
Webb, Katharine J.
Uhr, Manfred
Refojo, Damian
Schmidt, Mathias V.
Friess, Elisabeth
Steiger, Axel
Kimura, Mayumi
Chen, Alon
Holsboer, Florian
Arzt, Eduardo Simon
Wurst, Wolfgang
Deussing, Jan M.
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv HUMANIZED MOUSE MODEL
MOOD DISORDER
P2X7 RECEPTOR
PURINERGIC SIGNALING
SLEEP
STRESS
topic HUMANIZED MOUSE MODEL
MOOD DISORDER
P2X7 RECEPTOR
PURINERGIC SIGNALING
SLEEP
STRESS
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv 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.
Fil: Metzger, Michael W.. Max Planck Institut Fur Psychiatrie; Alemania
Fil: Walser, Sandra M.. Max Planck Institut Fur Psychiatrie; Alemania
Fil: Dedic, Nina. Max Planck Institut Fur Psychiatrie; Alemania
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
Fil: Jakubcakova, Vladimira. Max Planck Institut Fur Psychiatrie; Alemania
Fil: Adamczyk, Marek. Max Planck Institut Fur Psychiatrie; Alemania
Fil: Webb, Katharine J.. Max Planck Institut Fur Psychiatrie; Alemania
Fil: Uhr, Manfred. Max Planck Institut Fur Psychiatrie; Alemania
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
Fil: Schmidt, Mathias V.. Max Planck Institut Fur Psychiatrie; Alemania
Fil: Friess, Elisabeth. Max Planck Institut Fur Psychiatrie; Alemania
Fil: Steiger, Axel. Max Planck Institut Fur Psychiatrie; Alemania
Fil: Kimura, Mayumi. Max Planck Institut Fur Psychiatrie; Alemania
Fil: Chen, Alon. Max Planck Institut Fur Psychiatrie; Alemania. Weizmann Institute of Science; Israel
Fil: Holsboer, Florian. Max Planck Institut Fur Psychiatrie; Alemania
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
Fil: Wurst, Wolfgang. Institute of Developmental Genetics; Alemania. Technische Universität München-Weihenstephan; Alemania. German Center for Neurodegenerative Diseases; Alemania. Universität München; Alemania
Fil: Deussing, Jan M.. Max Planck Institut Fur Psychiatrie; Alemania
description 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.
publishDate 2017
dc.date.none.fl_str_mv 2017-11
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/55204
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
0270-6474
CONICET Digital
CONICET
url http://hdl.handle.net/11336/55204
identifier_str_mv 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
0270-6474
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1523/JNEUROSCI.3487-16.2017
info:eu-repo/semantics/altIdentifier/url/http://www.jneurosci.org/content/37/48/11688
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Society for Neuroscience
publisher.none.fl_str_mv Society for Neuroscience
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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score 13.070432

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