The indirect basal ganglia pathway in dopamine D2 receptor-deficient mice

Autores
Murer, Mario Gustavo; Dziewczapolski, G.; Salin, P.; Vila, M.; Tseng, Kuei y; Ruberg, M.; Rubinstein, Marcelo; Kelly, M. A.; Grandy, D. K.; Low, Malcolm J.; Hirsch, E.; Raisman Vozari, Rita; Gershanik, Oscar Samuel
Año de publicación
2000
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Recent pathophysiological models of basal ganglia function in Parkinson's disease predict that specific neurochemical changes in the indirect pathway would follow the lack of stimulation of D2 dopamine receptors. Post mortem studies of the basal ganglia in genetically modified mice lacking functional copies of the D2 dopamine receptor gene allowed us to test these predictions. When compared with their congenic N5 wild-type siblings, mice lacking D2 receptors show an increased expression of enkephalin messenger RNA in the striatum, and an increased activity and expression of cytochrome oxidase I in the subthalamic nucleus, as expected. In addition, D2 receptor-deficient mice display a reduced expression of glutamate decarboxylase-67 messenger RNA in the globus pallidus, as the basal ganglia model predicts. This reduction contrasts with the lack of change or increase in glutamate decarboxylase-67 messenger RNA expression found in animals depleted of dopamine after lesions of the mesostriatal dopaminergic system. Furthermore, D2 receptor-deficient mice show a significant decrease in substance P messenger RNA expression in the striatonigral neurons which form the direct pathway. Finally, glutamate decarboxylase-67 messenger RNA expression in the basal ganglia output nuclei was not affected by mutations in the D2 receptor gene, a fact that could probably be related to the absence of a parkinsonian locomotor phenotype in D2 receptor-deficient mice. In summary, these findings provide compelling evidence demonstrating that the lack of endogenous stimulation of D2 receptors is sufficient to produce subthalamic nucleus hyperactivity, as assessed by cytochrome oxidase I histochemistry and messenger RNA expression, and strongly suggest the existence of interactions between the basal ganglia direct and indirect pathways. (C) 2000 IBRO.
Fil: Murer, Mario Gustavo. Inserm; Francia. 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: Dziewczapolski, G.. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Farmacológicas. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Investigaciones Farmacológicas; Argentina
Fil: Salin, P.. Centre National de la Recherche Scientifique; Francia
Fil: Vila, M.. Inserm; Francia
Fil: Tseng, Kuei y. Universidad de Buenos Aires. Facultad de Medicina; Argentina
Fil: Ruberg, M.. Inserm; Francia
Fil: Rubinstein, Marcelo. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina
Fil: Kelly, M. A.. University of Oregon; Estados Unidos
Fil: Grandy, D. K.. University of Oregon; Estados Unidos
Fil: Low, M. J.. University of Oregon; Estados Unidos
Fil: Hirsch, E.. Inserm; Francia
Fil: Raisman Vozari, Rita. Inserm; Francia
Fil: Gershanik, Oscar Samuel. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Ciencias Biológicas; Argentina
Materia
Globus Pallidus
Parkinson'S Disease
Striatum
Substantia Nigra
Subthalamic Nucleus
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:11336/39164
Acceder
id CONICETDig_8059d907733a74697d29835f4c07628d
oai_identifier_str oai:ri.conicet.gov.ar:11336/39164
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling The indirect basal ganglia pathway in dopamine D2 receptor-deficient miceMurer, Mario GustavoDziewczapolski, G.Salin, P.Vila, M.Tseng, Kuei yRuberg, M.Rubinstein, MarceloKelly, M. A.Grandy, D. K.Low, Malcolm J.Hirsch, E.Raisman Vozari, RitaGershanik, Oscar SamuelGlobus PallidusParkinson'S DiseaseStriatumSubstantia NigraSubthalamic Nucleushttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3Recent pathophysiological models of basal ganglia function in Parkinson's disease predict that specific neurochemical changes in the indirect pathway would follow the lack of stimulation of D2 dopamine receptors. Post mortem studies of the basal ganglia in genetically modified mice lacking functional copies of the D2 dopamine receptor gene allowed us to test these predictions. When compared with their congenic N5 wild-type siblings, mice lacking D2 receptors show an increased expression of enkephalin messenger RNA in the striatum, and an increased activity and expression of cytochrome oxidase I in the subthalamic nucleus, as expected. In addition, D2 receptor-deficient mice display a reduced expression of glutamate decarboxylase-67 messenger RNA in the globus pallidus, as the basal ganglia model predicts. This reduction contrasts with the lack of change or increase in glutamate decarboxylase-67 messenger RNA expression found in animals depleted of dopamine after lesions of the mesostriatal dopaminergic system. Furthermore, D2 receptor-deficient mice show a significant decrease in substance P messenger RNA expression in the striatonigral neurons which form the direct pathway. Finally, glutamate decarboxylase-67 messenger RNA expression in the basal ganglia output nuclei was not affected by mutations in the D2 receptor gene, a fact that could probably be related to the absence of a parkinsonian locomotor phenotype in D2 receptor-deficient mice. In summary, these findings provide compelling evidence demonstrating that the lack of endogenous stimulation of D2 receptors is sufficient to produce subthalamic nucleus hyperactivity, as assessed by cytochrome oxidase I histochemistry and messenger RNA expression, and strongly suggest the existence of interactions between the basal ganglia direct and indirect pathways. (C) 2000 IBRO.Fil: Murer, Mario Gustavo. Inserm; Francia. 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: Dziewczapolski, G.. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Farmacológicas. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Investigaciones Farmacológicas; ArgentinaFil: Salin, P.. Centre National de la Recherche Scientifique; FranciaFil: Vila, M.. Inserm; FranciaFil: Tseng, Kuei y. Universidad de Buenos Aires. Facultad de Medicina; ArgentinaFil: Ruberg, M.. Inserm; FranciaFil: Rubinstein, Marcelo. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; ArgentinaFil: Kelly, M. A.. University of Oregon; Estados UnidosFil: Grandy, D. K.. University of Oregon; Estados UnidosFil: Low, M. J.. University of Oregon; Estados UnidosFil: Hirsch, E.. Inserm; FranciaFil: Raisman Vozari, Rita. Inserm; FranciaFil: Gershanik, Oscar Samuel. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Ciencias Biológicas; ArgentinaPergamon-Elsevier Science Ltd2000-08info: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/11336/39164Murer, Mario Gustavo; Dziewczapolski, G.; Salin, P.; Vila, M.; Tseng, Kuei y; et al.; The indirect basal ganglia pathway in dopamine D2 receptor-deficient mice; Pergamon-Elsevier Science Ltd; Neuroscience; 99; 4; 8-2000; 643-6500306-4522CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1016/S0306-4522(00)00223-2info:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/pii/S0306452200002232info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T09:57:49Zoai:ri.conicet.gov.ar:11336/39164instacron: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:34982025-09-03 09:57:49.489CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv The indirect basal ganglia pathway in dopamine D2 receptor-deficient mice
title The indirect basal ganglia pathway in dopamine D2 receptor-deficient mice
spellingShingle The indirect basal ganglia pathway in dopamine D2 receptor-deficient mice
Murer, Mario Gustavo
Globus Pallidus
Parkinson'S Disease
Striatum
Substantia Nigra
Subthalamic Nucleus
title_short The indirect basal ganglia pathway in dopamine D2 receptor-deficient mice
title_full The indirect basal ganglia pathway in dopamine D2 receptor-deficient mice
title_fullStr The indirect basal ganglia pathway in dopamine D2 receptor-deficient mice
title_full_unstemmed The indirect basal ganglia pathway in dopamine D2 receptor-deficient mice
title_sort The indirect basal ganglia pathway in dopamine D2 receptor-deficient mice
dc.creator.none.fl_str_mv Murer, Mario Gustavo
Dziewczapolski, G.
Salin, P.
Vila, M.
Tseng, Kuei y
Ruberg, M.
Rubinstein, Marcelo
Kelly, M. A.
Grandy, D. K.
Low, Malcolm J.
Hirsch, E.
Raisman Vozari, Rita
Gershanik, Oscar Samuel
author Murer, Mario Gustavo
author_facet Murer, Mario Gustavo
Dziewczapolski, G.
Salin, P.
Vila, M.
Tseng, Kuei y
Ruberg, M.
Rubinstein, Marcelo
Kelly, M. A.
Grandy, D. K.
Low, Malcolm J.
Hirsch, E.
Raisman Vozari, Rita
Gershanik, Oscar Samuel
author_role author
author2 Dziewczapolski, G.
Salin, P.
Vila, M.
Tseng, Kuei y
Ruberg, M.
Rubinstein, Marcelo
Kelly, M. A.
Grandy, D. K.
Low, Malcolm J.
Hirsch, E.
Raisman Vozari, Rita
Gershanik, Oscar Samuel
author2_role author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Globus Pallidus
Parkinson'S Disease
Striatum
Substantia Nigra
Subthalamic Nucleus
topic Globus Pallidus
Parkinson'S Disease
Striatum
Substantia Nigra
Subthalamic Nucleus
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Recent pathophysiological models of basal ganglia function in Parkinson's disease predict that specific neurochemical changes in the indirect pathway would follow the lack of stimulation of D2 dopamine receptors. Post mortem studies of the basal ganglia in genetically modified mice lacking functional copies of the D2 dopamine receptor gene allowed us to test these predictions. When compared with their congenic N5 wild-type siblings, mice lacking D2 receptors show an increased expression of enkephalin messenger RNA in the striatum, and an increased activity and expression of cytochrome oxidase I in the subthalamic nucleus, as expected. In addition, D2 receptor-deficient mice display a reduced expression of glutamate decarboxylase-67 messenger RNA in the globus pallidus, as the basal ganglia model predicts. This reduction contrasts with the lack of change or increase in glutamate decarboxylase-67 messenger RNA expression found in animals depleted of dopamine after lesions of the mesostriatal dopaminergic system. Furthermore, D2 receptor-deficient mice show a significant decrease in substance P messenger RNA expression in the striatonigral neurons which form the direct pathway. Finally, glutamate decarboxylase-67 messenger RNA expression in the basal ganglia output nuclei was not affected by mutations in the D2 receptor gene, a fact that could probably be related to the absence of a parkinsonian locomotor phenotype in D2 receptor-deficient mice. In summary, these findings provide compelling evidence demonstrating that the lack of endogenous stimulation of D2 receptors is sufficient to produce subthalamic nucleus hyperactivity, as assessed by cytochrome oxidase I histochemistry and messenger RNA expression, and strongly suggest the existence of interactions between the basal ganglia direct and indirect pathways. (C) 2000 IBRO.
Fil: Murer, Mario Gustavo. Inserm; Francia. 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: Dziewczapolski, G.. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Farmacológicas. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Investigaciones Farmacológicas; Argentina
Fil: Salin, P.. Centre National de la Recherche Scientifique; Francia
Fil: Vila, M.. Inserm; Francia
Fil: Tseng, Kuei y. Universidad de Buenos Aires. Facultad de Medicina; Argentina
Fil: Ruberg, M.. Inserm; Francia
Fil: Rubinstein, Marcelo. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina
Fil: Kelly, M. A.. University of Oregon; Estados Unidos
Fil: Grandy, D. K.. University of Oregon; Estados Unidos
Fil: Low, M. J.. University of Oregon; Estados Unidos
Fil: Hirsch, E.. Inserm; Francia
Fil: Raisman Vozari, Rita. Inserm; Francia
Fil: Gershanik, Oscar Samuel. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Ciencias Biológicas; Argentina
description Recent pathophysiological models of basal ganglia function in Parkinson's disease predict that specific neurochemical changes in the indirect pathway would follow the lack of stimulation of D2 dopamine receptors. Post mortem studies of the basal ganglia in genetically modified mice lacking functional copies of the D2 dopamine receptor gene allowed us to test these predictions. When compared with their congenic N5 wild-type siblings, mice lacking D2 receptors show an increased expression of enkephalin messenger RNA in the striatum, and an increased activity and expression of cytochrome oxidase I in the subthalamic nucleus, as expected. In addition, D2 receptor-deficient mice display a reduced expression of glutamate decarboxylase-67 messenger RNA in the globus pallidus, as the basal ganglia model predicts. This reduction contrasts with the lack of change or increase in glutamate decarboxylase-67 messenger RNA expression found in animals depleted of dopamine after lesions of the mesostriatal dopaminergic system. Furthermore, D2 receptor-deficient mice show a significant decrease in substance P messenger RNA expression in the striatonigral neurons which form the direct pathway. Finally, glutamate decarboxylase-67 messenger RNA expression in the basal ganglia output nuclei was not affected by mutations in the D2 receptor gene, a fact that could probably be related to the absence of a parkinsonian locomotor phenotype in D2 receptor-deficient mice. In summary, these findings provide compelling evidence demonstrating that the lack of endogenous stimulation of D2 receptors is sufficient to produce subthalamic nucleus hyperactivity, as assessed by cytochrome oxidase I histochemistry and messenger RNA expression, and strongly suggest the existence of interactions between the basal ganglia direct and indirect pathways. (C) 2000 IBRO.
publishDate 2000
dc.date.none.fl_str_mv 2000-08
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/11336/39164
Murer, Mario Gustavo; Dziewczapolski, G.; Salin, P.; Vila, M.; Tseng, Kuei y; et al.; The indirect basal ganglia pathway in dopamine D2 receptor-deficient mice; Pergamon-Elsevier Science Ltd; Neuroscience; 99; 4; 8-2000; 643-650
0306-4522
CONICET Digital
CONICET
url http://hdl.handle.net/11336/39164
identifier_str_mv Murer, Mario Gustavo; Dziewczapolski, G.; Salin, P.; Vila, M.; Tseng, Kuei y; et al.; The indirect basal ganglia pathway in dopamine D2 receptor-deficient mice; Pergamon-Elsevier Science Ltd; Neuroscience; 99; 4; 8-2000; 643-650
0306-4522
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1016/S0306-4522(00)00223-2
info:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/pii/S0306452200002232
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 Pergamon-Elsevier Science Ltd
publisher.none.fl_str_mv Pergamon-Elsevier Science Ltd
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 13.13397

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