D2 dopamine receptors and the striatopallidal pathway modulate L-DOPA-induced dyskinesia in the mouse

Autores
Sáez, María; Keifman, Ettel; Alberquilla, Samuel; Coll, Camila; Reig, Ramón; Murer, Mario Gustavo; Moratalla, Rosario
Año de publicación
2023
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
L-DOPA-induced dyskinesia (LID) remains a major complication of Parkinson's disease management for which better therapies are necessary. The contribution of the striatonigral direct pathway to LID is widely acknowledged but whether the striatopallidal pathway is involved remains debated. Selective optogenetic stimulation of striatonigral axon terminals induces dyskinesia in mice rendered hemiparkinsonian with the toxin 6-hydroxydopamine (6-OHDA). Here we show that optogenetically-induced dyskinesia is increased by the D2-type dopamine receptor agonist quinpirole. Although the quinpirole effect may be mediated by D2 receptor stimulation in striatopallidal neurons, alternative mechanisms may be responsible as well. To selectively modulate the striatopallidal pathway, we selectively expressed channelrhodopsin-2 (ChR2) in D2 receptor expressing neurons by crossing D2-Cre and ChR2-flox mice. The animals were rendered hemiparkinsonian and implanted with an optic fiber at the ipsilateral external globus pallidus (GPe). Stimulation of ChR2 at striatopallidal axon terminals reduced LID and also general motility during the off L-DOPA state, without modifying the pro-motor effect of low doses of L-DOPA producing mild or no dyskinesia. Overall, the present study shows that D2-type dopamine receptors and the striatopallidal pathway modulate dyskinesia and suggest that targeting striatopallidal axon terminals at the GPe may have therapeutic potential in the management of LID.
Fil: Sáez, María. Consejo Superior de Investigaciones Científicas. Instituto Cajal; . Consejo Superior de Investigaciones Científicas. Instituto de Neurociencia de Alicante; España
Fil: Keifman, Ettel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Fisiología y Biofísica Bernardo Houssay. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiología y Biofísica Bernardo Houssay; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Ciencias Fisiológicas; Argentina
Fil: Alberquilla, Samuel. Consejo Superior de Investigaciones Científicas. Instituto Cajal; . Instituto de Salud Carlos III; España
Fil: Coll, Camila. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Fisiología y Biofísica Bernardo Houssay. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiología y Biofísica Bernardo Houssay; Argentina
Fil: Reig, Ramón. Consejo Superior de Investigaciones Científicas. Instituto de Neurociencia de Alicante; España
Fil: Murer, Mario Gustavo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Fisiología y Biofísica Bernardo Houssay. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiología y Biofísica Bernardo Houssay; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Ciencias Fisiológicas; Argentina
Fil: Moratalla, Rosario. Consejo Superior de Investigaciones Científicas. Instituto Cajal; . Instituto de Salud Carlos III; España
Materia
INDIRECT BASAL GANGLIA PATHWAY
L-DOPA-INDUCED DYSKINESIA
OPTOGENETICS
PARKINSON'S DISEASE
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/227826
Acceder
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repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling D2 dopamine receptors and the striatopallidal pathway modulate L-DOPA-induced dyskinesia in the mouseSáez, MaríaKeifman, EttelAlberquilla, SamuelColl, CamilaReig, RamónMurer, Mario GustavoMoratalla, RosarioINDIRECT BASAL GANGLIA PATHWAYL-DOPA-INDUCED DYSKINESIAOPTOGENETICSPARKINSON'S DISEASEhttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3L-DOPA-induced dyskinesia (LID) remains a major complication of Parkinson's disease management for which better therapies are necessary. The contribution of the striatonigral direct pathway to LID is widely acknowledged but whether the striatopallidal pathway is involved remains debated. Selective optogenetic stimulation of striatonigral axon terminals induces dyskinesia in mice rendered hemiparkinsonian with the toxin 6-hydroxydopamine (6-OHDA). Here we show that optogenetically-induced dyskinesia is increased by the D2-type dopamine receptor agonist quinpirole. Although the quinpirole effect may be mediated by D2 receptor stimulation in striatopallidal neurons, alternative mechanisms may be responsible as well. To selectively modulate the striatopallidal pathway, we selectively expressed channelrhodopsin-2 (ChR2) in D2 receptor expressing neurons by crossing D2-Cre and ChR2-flox mice. The animals were rendered hemiparkinsonian and implanted with an optic fiber at the ipsilateral external globus pallidus (GPe). Stimulation of ChR2 at striatopallidal axon terminals reduced LID and also general motility during the off L-DOPA state, without modifying the pro-motor effect of low doses of L-DOPA producing mild or no dyskinesia. Overall, the present study shows that D2-type dopamine receptors and the striatopallidal pathway modulate dyskinesia and suggest that targeting striatopallidal axon terminals at the GPe may have therapeutic potential in the management of LID.Fil: Sáez, María. Consejo Superior de Investigaciones Científicas. Instituto Cajal; . Consejo Superior de Investigaciones Científicas. Instituto de Neurociencia de Alicante; EspañaFil: Keifman, Ettel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Fisiología y Biofísica Bernardo Houssay. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiología y Biofísica Bernardo Houssay; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Ciencias Fisiológicas; ArgentinaFil: Alberquilla, Samuel. Consejo Superior de Investigaciones Científicas. Instituto Cajal; . Instituto de Salud Carlos III; EspañaFil: Coll, Camila. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Fisiología y Biofísica Bernardo Houssay. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiología y Biofísica Bernardo Houssay; ArgentinaFil: Reig, Ramón. Consejo Superior de Investigaciones Científicas. Instituto de Neurociencia de Alicante; EspañaFil: Murer, Mario Gustavo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Fisiología y Biofísica Bernardo Houssay. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiología y Biofísica Bernardo Houssay; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Ciencias Fisiológicas; ArgentinaFil: Moratalla, Rosario. Consejo Superior de Investigaciones Científicas. Instituto Cajal; . Instituto de Salud Carlos III; EspañaAcademic Press Inc Elsevier Science2023-10info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/vnd.openxmlformats-officedocument.wordprocessingml.documentapplication/pdfhttp://hdl.handle.net/11336/227826Sáez, María; Keifman, Ettel; Alberquilla, Samuel; Coll, Camila; Reig, Ramón; et al.; D2 dopamine receptors and the striatopallidal pathway modulate L-DOPA-induced dyskinesia in the mouse; Academic Press Inc Elsevier Science; Neurobiology of Disease; 186; 10-2023; 1-100969-9961CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/pii/S0969996123002930info:eu-repo/semantics/altIdentifier/doi/10.1016/j.nbd.2023.106278info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-nd/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-10T13:24:33Zoai:ri.conicet.gov.ar:11336/227826instacron: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:34982025-09-10 13:24:33.365CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv D2 dopamine receptors and the striatopallidal pathway modulate L-DOPA-induced dyskinesia in the mouse
title D2 dopamine receptors and the striatopallidal pathway modulate L-DOPA-induced dyskinesia in the mouse
spellingShingle D2 dopamine receptors and the striatopallidal pathway modulate L-DOPA-induced dyskinesia in the mouse
Sáez, María
INDIRECT BASAL GANGLIA PATHWAY
L-DOPA-INDUCED DYSKINESIA
OPTOGENETICS
PARKINSON'S DISEASE
title_short D2 dopamine receptors and the striatopallidal pathway modulate L-DOPA-induced dyskinesia in the mouse
title_full D2 dopamine receptors and the striatopallidal pathway modulate L-DOPA-induced dyskinesia in the mouse
title_fullStr D2 dopamine receptors and the striatopallidal pathway modulate L-DOPA-induced dyskinesia in the mouse
title_full_unstemmed D2 dopamine receptors and the striatopallidal pathway modulate L-DOPA-induced dyskinesia in the mouse
title_sort D2 dopamine receptors and the striatopallidal pathway modulate L-DOPA-induced dyskinesia in the mouse
dc.creator.none.fl_str_mv Sáez, María
Keifman, Ettel
Alberquilla, Samuel
Coll, Camila
Reig, Ramón
Murer, Mario Gustavo
Moratalla, Rosario
author Sáez, María
author_facet Sáez, María
Keifman, Ettel
Alberquilla, Samuel
Coll, Camila
Reig, Ramón
Murer, Mario Gustavo
Moratalla, Rosario
author_role author
author2 Keifman, Ettel
Alberquilla, Samuel
Coll, Camila
Reig, Ramón
Murer, Mario Gustavo
Moratalla, Rosario
author2_role author
author
author
author
author
author
dc.subject.none.fl_str_mv INDIRECT BASAL GANGLIA PATHWAY
L-DOPA-INDUCED DYSKINESIA
OPTOGENETICS
PARKINSON'S DISEASE
topic INDIRECT BASAL GANGLIA PATHWAY
L-DOPA-INDUCED DYSKINESIA
OPTOGENETICS
PARKINSON'S DISEASE
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv L-DOPA-induced dyskinesia (LID) remains a major complication of Parkinson's disease management for which better therapies are necessary. The contribution of the striatonigral direct pathway to LID is widely acknowledged but whether the striatopallidal pathway is involved remains debated. Selective optogenetic stimulation of striatonigral axon terminals induces dyskinesia in mice rendered hemiparkinsonian with the toxin 6-hydroxydopamine (6-OHDA). Here we show that optogenetically-induced dyskinesia is increased by the D2-type dopamine receptor agonist quinpirole. Although the quinpirole effect may be mediated by D2 receptor stimulation in striatopallidal neurons, alternative mechanisms may be responsible as well. To selectively modulate the striatopallidal pathway, we selectively expressed channelrhodopsin-2 (ChR2) in D2 receptor expressing neurons by crossing D2-Cre and ChR2-flox mice. The animals were rendered hemiparkinsonian and implanted with an optic fiber at the ipsilateral external globus pallidus (GPe). Stimulation of ChR2 at striatopallidal axon terminals reduced LID and also general motility during the off L-DOPA state, without modifying the pro-motor effect of low doses of L-DOPA producing mild or no dyskinesia. Overall, the present study shows that D2-type dopamine receptors and the striatopallidal pathway modulate dyskinesia and suggest that targeting striatopallidal axon terminals at the GPe may have therapeutic potential in the management of LID.
Fil: Sáez, María. Consejo Superior de Investigaciones Científicas. Instituto Cajal; . Consejo Superior de Investigaciones Científicas. Instituto de Neurociencia de Alicante; España
Fil: Keifman, Ettel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Fisiología y Biofísica Bernardo Houssay. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiología y Biofísica Bernardo Houssay; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Ciencias Fisiológicas; Argentina
Fil: Alberquilla, Samuel. Consejo Superior de Investigaciones Científicas. Instituto Cajal; . Instituto de Salud Carlos III; España
Fil: Coll, Camila. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Fisiología y Biofísica Bernardo Houssay. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiología y Biofísica Bernardo Houssay; Argentina
Fil: Reig, Ramón. Consejo Superior de Investigaciones Científicas. Instituto de Neurociencia de Alicante; España
Fil: Murer, Mario Gustavo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Fisiología y Biofísica Bernardo Houssay. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiología y Biofísica Bernardo Houssay; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Ciencias Fisiológicas; Argentina
Fil: Moratalla, Rosario. Consejo Superior de Investigaciones Científicas. Instituto Cajal; . Instituto de Salud Carlos III; España
description L-DOPA-induced dyskinesia (LID) remains a major complication of Parkinson's disease management for which better therapies are necessary. The contribution of the striatonigral direct pathway to LID is widely acknowledged but whether the striatopallidal pathway is involved remains debated. Selective optogenetic stimulation of striatonigral axon terminals induces dyskinesia in mice rendered hemiparkinsonian with the toxin 6-hydroxydopamine (6-OHDA). Here we show that optogenetically-induced dyskinesia is increased by the D2-type dopamine receptor agonist quinpirole. Although the quinpirole effect may be mediated by D2 receptor stimulation in striatopallidal neurons, alternative mechanisms may be responsible as well. To selectively modulate the striatopallidal pathway, we selectively expressed channelrhodopsin-2 (ChR2) in D2 receptor expressing neurons by crossing D2-Cre and ChR2-flox mice. The animals were rendered hemiparkinsonian and implanted with an optic fiber at the ipsilateral external globus pallidus (GPe). Stimulation of ChR2 at striatopallidal axon terminals reduced LID and also general motility during the off L-DOPA state, without modifying the pro-motor effect of low doses of L-DOPA producing mild or no dyskinesia. Overall, the present study shows that D2-type dopamine receptors and the striatopallidal pathway modulate dyskinesia and suggest that targeting striatopallidal axon terminals at the GPe may have therapeutic potential in the management of LID.
publishDate 2023
dc.date.none.fl_str_mv 2023-10
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/11336/227826
Sáez, María; Keifman, Ettel; Alberquilla, Samuel; Coll, Camila; Reig, Ramón; et al.; D2 dopamine receptors and the striatopallidal pathway modulate L-DOPA-induced dyskinesia in the mouse; Academic Press Inc Elsevier Science; Neurobiology of Disease; 186; 10-2023; 1-10
0969-9961
CONICET Digital
CONICET
url http://hdl.handle.net/11336/227826
identifier_str_mv Sáez, María; Keifman, Ettel; Alberquilla, Samuel; Coll, Camila; Reig, Ramón; et al.; D2 dopamine receptors and the striatopallidal pathway modulate L-DOPA-induced dyskinesia in the mouse; Academic Press Inc Elsevier Science; Neurobiology of Disease; 186; 10-2023; 1-10
0969-9961
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.sciencedirect.com/science/article/pii/S0969996123002930
info:eu-repo/semantics/altIdentifier/doi/10.1016/j.nbd.2023.106278
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/vnd.openxmlformats-officedocument.wordprocessingml.document
application/pdf
dc.publisher.none.fl_str_mv Academic Press Inc Elsevier Science
publisher.none.fl_str_mv Academic Press Inc Elsevier Science
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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