A viral vector model for circuit-specific synucleinopathy

Autores
Lantheaume, Alexia; Schöneberg, Nina; Rodriguez Rozada, Silvia; Doll, Dennis; Schellenberger, Michael; Kobel, Konstantin; Katzenberge, Kilian; Signoret Genest, Jérémy; Tissone, Angela Isabel; Ip, Chi Wang; Esposito, Maria Soledad; Tovote, Philip
Año de publicación
2023
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
In Parkinson's disease (PD), pathomechanisms such as aberrant network dysfunctions can be elucidated by conducting multiscale explorations in animal models. However, the lack of specificity in the existing models limits a restricted targeting of individual network elements and characterization of PD as a “circuitopathy”. We therefore developed a cell-type specific viral vector (AAV2/9-CreON-A53T-αSyn) mouse model that allows to induce synucleinopathy within individual circuit elements in vivo. When specifically targeted to dopaminergic (DA) neurons of the substantia nigra pars compacta (SNc), our approach recapitulates the main hallmarks of the disease, namely Lewy-body-like aggregation, progressive cellular and nigrostriatal projections loss, together with locomotor impairment. Our strategy is supported by new state-of-the-art analytical approaches for cell quantification and behavior characterization. Altogether, we provide a novel model of synucleinopathy, which offers new opportunities to study the contribution of individual network elements to disease pathomechanisms.
Fil: Lantheaume, Alexia. Universität Würzburg; Alemania
Fil: Schöneberg, Nina. Universität Würzburg; Alemania
Fil: Rodriguez Rozada, Silvia. Universität Würzburg; Alemania
Fil: Doll, Dennis. Universität Würzburg; Alemania
Fil: Schellenberger, Michael. Universität Würzburg; Alemania
Fil: Kobel, Konstantin. Universität Würzburg; Alemania
Fil: Katzenberge, Kilian. Universität Würzburg; Alemania
Fil: Signoret Genest, Jérémy. Universität Würzburg; Alemania
Fil: Tissone, Angela Isabel. Comisión Nacional de Energía Atómica. Gerencia del Área de Energía Nuclear. Instituto Balseiro. Archivo Histórico del Centro Atómico Bariloche e Instituto Balseiro | Universidad Nacional de Cuyo. Instituto Balseiro. Archivo Histórico del Centro Atómico Bariloche e Instituto Balseiro; Argentina
Fil: Ip, Chi Wang. Universität Würzburg; Alemania
Fil: Esposito, Maria Soledad. Comisión Nacional de Energía Atómica. Gerencia del Área de Energía Nuclear. Instituto Balseiro. Archivo Histórico del Centro Atómico Bariloche e Instituto Balseiro | Universidad Nacional de Cuyo. Instituto Balseiro. Archivo Histórico del Centro Atómico Bariloche e Instituto Balseiro; Argentina
Fil: Tovote, Philip. Universität Würzburg; Alemania
Materia
Parkinson's disease
AAV
alphasynuclein
cell-type specificity
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:11336/240536
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/240536
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling A viral vector model for circuit-specific synucleinopathyLantheaume, AlexiaSchöneberg, NinaRodriguez Rozada, SilviaDoll, DennisSchellenberger, MichaelKobel, KonstantinKatzenberge, KilianSignoret Genest, JérémyTissone, Angela IsabelIp, Chi WangEsposito, Maria SoledadTovote, PhilipParkinson's diseaseAAValphasynucleincell-type specificityhttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3In Parkinson's disease (PD), pathomechanisms such as aberrant network dysfunctions can be elucidated by conducting multiscale explorations in animal models. However, the lack of specificity in the existing models limits a restricted targeting of individual network elements and characterization of PD as a “circuitopathy”. We therefore developed a cell-type specific viral vector (AAV2/9-CreON-A53T-αSyn) mouse model that allows to induce synucleinopathy within individual circuit elements in vivo. When specifically targeted to dopaminergic (DA) neurons of the substantia nigra pars compacta (SNc), our approach recapitulates the main hallmarks of the disease, namely Lewy-body-like aggregation, progressive cellular and nigrostriatal projections loss, together with locomotor impairment. Our strategy is supported by new state-of-the-art analytical approaches for cell quantification and behavior characterization. Altogether, we provide a novel model of synucleinopathy, which offers new opportunities to study the contribution of individual network elements to disease pathomechanisms.Fil: Lantheaume, Alexia. Universität Würzburg; AlemaniaFil: Schöneberg, Nina. Universität Würzburg; AlemaniaFil: Rodriguez Rozada, Silvia. Universität Würzburg; AlemaniaFil: Doll, Dennis. Universität Würzburg; AlemaniaFil: Schellenberger, Michael. Universität Würzburg; AlemaniaFil: Kobel, Konstantin. Universität Würzburg; AlemaniaFil: Katzenberge, Kilian. Universität Würzburg; AlemaniaFil: Signoret Genest, Jérémy. Universität Würzburg; AlemaniaFil: Tissone, Angela Isabel. Comisión Nacional de Energía Atómica. Gerencia del Área de Energía Nuclear. Instituto Balseiro. Archivo Histórico del Centro Atómico Bariloche e Instituto Balseiro | Universidad Nacional de Cuyo. Instituto Balseiro. Archivo Histórico del Centro Atómico Bariloche e Instituto Balseiro; ArgentinaFil: Ip, Chi Wang. Universität Würzburg; AlemaniaFil: Esposito, Maria Soledad. Comisión Nacional de Energía Atómica. Gerencia del Área de Energía Nuclear. Instituto Balseiro. Archivo Histórico del Centro Atómico Bariloche e Instituto Balseiro | Universidad Nacional de Cuyo. Instituto Balseiro. Archivo Histórico del Centro Atómico Bariloche e Instituto Balseiro; ArgentinaFil: Tovote, Philip. Universität Würzburg; AlemaniaCold Spring Harbor Laboratory Press2023-08info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/240536Lantheaume, Alexia; Schöneberg, Nina; Rodriguez Rozada, Silvia; Doll, Dennis; Schellenberger, Michael; et al.; A viral vector model for circuit-specific synucleinopathy; Cold Spring Harbor Laboratory Press; bioRxiV; 2023; 8-2023; 1-222692-8205CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.biorxiv.org/content/10.1101/2023.08.28.555129v1info:eu-repo/semantics/altIdentifier/doi/10.1101/2023.08.28.555129info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T10:20:16Zoai:ri.conicet.gov.ar:11336/240536instacron: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 10:20:16.901CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv A viral vector model for circuit-specific synucleinopathy
title A viral vector model for circuit-specific synucleinopathy
spellingShingle A viral vector model for circuit-specific synucleinopathy
Lantheaume, Alexia
Parkinson's disease
AAV
alphasynuclein
cell-type specificity
title_short A viral vector model for circuit-specific synucleinopathy
title_full A viral vector model for circuit-specific synucleinopathy
title_fullStr A viral vector model for circuit-specific synucleinopathy
title_full_unstemmed A viral vector model for circuit-specific synucleinopathy
title_sort A viral vector model for circuit-specific synucleinopathy
dc.creator.none.fl_str_mv Lantheaume, Alexia
Schöneberg, Nina
Rodriguez Rozada, Silvia
Doll, Dennis
Schellenberger, Michael
Kobel, Konstantin
Katzenberge, Kilian
Signoret Genest, Jérémy
Tissone, Angela Isabel
Ip, Chi Wang
Esposito, Maria Soledad
Tovote, Philip
author Lantheaume, Alexia
author_facet Lantheaume, Alexia
Schöneberg, Nina
Rodriguez Rozada, Silvia
Doll, Dennis
Schellenberger, Michael
Kobel, Konstantin
Katzenberge, Kilian
Signoret Genest, Jérémy
Tissone, Angela Isabel
Ip, Chi Wang
Esposito, Maria Soledad
Tovote, Philip
author_role author
author2 Schöneberg, Nina
Rodriguez Rozada, Silvia
Doll, Dennis
Schellenberger, Michael
Kobel, Konstantin
Katzenberge, Kilian
Signoret Genest, Jérémy
Tissone, Angela Isabel
Ip, Chi Wang
Esposito, Maria Soledad
Tovote, Philip
author2_role author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Parkinson's disease
AAV
alphasynuclein
cell-type specificity
topic Parkinson's disease
AAV
alphasynuclein
cell-type specificity
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv In Parkinson's disease (PD), pathomechanisms such as aberrant network dysfunctions can be elucidated by conducting multiscale explorations in animal models. However, the lack of specificity in the existing models limits a restricted targeting of individual network elements and characterization of PD as a “circuitopathy”. We therefore developed a cell-type specific viral vector (AAV2/9-CreON-A53T-αSyn) mouse model that allows to induce synucleinopathy within individual circuit elements in vivo. When specifically targeted to dopaminergic (DA) neurons of the substantia nigra pars compacta (SNc), our approach recapitulates the main hallmarks of the disease, namely Lewy-body-like aggregation, progressive cellular and nigrostriatal projections loss, together with locomotor impairment. Our strategy is supported by new state-of-the-art analytical approaches for cell quantification and behavior characterization. Altogether, we provide a novel model of synucleinopathy, which offers new opportunities to study the contribution of individual network elements to disease pathomechanisms.
Fil: Lantheaume, Alexia. Universität Würzburg; Alemania
Fil: Schöneberg, Nina. Universität Würzburg; Alemania
Fil: Rodriguez Rozada, Silvia. Universität Würzburg; Alemania
Fil: Doll, Dennis. Universität Würzburg; Alemania
Fil: Schellenberger, Michael. Universität Würzburg; Alemania
Fil: Kobel, Konstantin. Universität Würzburg; Alemania
Fil: Katzenberge, Kilian. Universität Würzburg; Alemania
Fil: Signoret Genest, Jérémy. Universität Würzburg; Alemania
Fil: Tissone, Angela Isabel. Comisión Nacional de Energía Atómica. Gerencia del Área de Energía Nuclear. Instituto Balseiro. Archivo Histórico del Centro Atómico Bariloche e Instituto Balseiro | Universidad Nacional de Cuyo. Instituto Balseiro. Archivo Histórico del Centro Atómico Bariloche e Instituto Balseiro; Argentina
Fil: Ip, Chi Wang. Universität Würzburg; Alemania
Fil: Esposito, Maria Soledad. Comisión Nacional de Energía Atómica. Gerencia del Área de Energía Nuclear. Instituto Balseiro. Archivo Histórico del Centro Atómico Bariloche e Instituto Balseiro | Universidad Nacional de Cuyo. Instituto Balseiro. Archivo Histórico del Centro Atómico Bariloche e Instituto Balseiro; Argentina
Fil: Tovote, Philip. Universität Würzburg; Alemania
description In Parkinson's disease (PD), pathomechanisms such as aberrant network dysfunctions can be elucidated by conducting multiscale explorations in animal models. However, the lack of specificity in the existing models limits a restricted targeting of individual network elements and characterization of PD as a “circuitopathy”. We therefore developed a cell-type specific viral vector (AAV2/9-CreON-A53T-αSyn) mouse model that allows to induce synucleinopathy within individual circuit elements in vivo. When specifically targeted to dopaminergic (DA) neurons of the substantia nigra pars compacta (SNc), our approach recapitulates the main hallmarks of the disease, namely Lewy-body-like aggregation, progressive cellular and nigrostriatal projections loss, together with locomotor impairment. Our strategy is supported by new state-of-the-art analytical approaches for cell quantification and behavior characterization. Altogether, we provide a novel model of synucleinopathy, which offers new opportunities to study the contribution of individual network elements to disease pathomechanisms.
publishDate 2023
dc.date.none.fl_str_mv 2023-08
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/11336/240536
Lantheaume, Alexia; Schöneberg, Nina; Rodriguez Rozada, Silvia; Doll, Dennis; Schellenberger, Michael; et al.; A viral vector model for circuit-specific synucleinopathy; Cold Spring Harbor Laboratory Press; bioRxiV; 2023; 8-2023; 1-22
2692-8205
CONICET Digital
CONICET
url http://hdl.handle.net/11336/240536
identifier_str_mv Lantheaume, Alexia; Schöneberg, Nina; Rodriguez Rozada, Silvia; Doll, Dennis; Schellenberger, Michael; et al.; A viral vector model for circuit-specific synucleinopathy; Cold Spring Harbor Laboratory Press; bioRxiV; 2023; 8-2023; 1-22
2692-8205
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/https://www.biorxiv.org/content/10.1101/2023.08.28.555129v1
info:eu-repo/semantics/altIdentifier/doi/10.1101/2023.08.28.555129
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
application/pdf
dc.publisher.none.fl_str_mv Cold Spring Harbor Laboratory Press
publisher.none.fl_str_mv Cold Spring Harbor Laboratory Press
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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