Tau dysfunction in the basal ganglia of a mouse model of tauopathy related to PSP

Autores
Damianich, Ana; Sartor, Manuela; Espindola, Sonia Lorena; Taravini, Irene Rita Eloisa; Gershanik, Oscar Samuel; Ferrario, Juan Esteban; Avale, Maria Elena
Año de publicación
2016
Idioma
inglés
Tipo de recurso
documento de conferencia
Estado
versión publicada
Descripción
Objective: Determine motor coordination and neurochemical phenotypes in the basal ganglia of mice lacking the Tau protein or expressing an abnormal content of Tau isoforms.Background: Microtubule-associated protein TAU is expressed in neurons and involved in microtubule polymerization and axonal transport. Tauopathies are neurodegenerative diseases, with presence of insoluble tau aggregates. Progressive Supranuclear Palsy (PSP) is a tauopathy that affects the basal ganglia thus leading PD symptoms. The pathological mechanisms of tauopathies have been extensively studied using animal models, mostly to analyze cognitive decline. Much less has been investigated about the role of normal and pathological Tau in the basal ganglia in those animal models. Here we investigated motor phenotypes and neurochemical changes in the striatum and substantia nigra pars compacta (SNpc) of mice lacking Tau (Tau KO) and in a mouse model of tauopathy (hTAU mice).Methods: We compared Wild type (WT), TauKO and hTAU mice in spontaneous locomotor activity in the open Öeld, motor coordination in the rotarod and cognitive performance in the novel object recognition task(NOR). Quantitation of dopaminergic (DA) neurons in the SNpc was done using stereology analysis.Dopamine and its metabolites were quantiÖed by HPLC. The relative amount of Tau isoforms was quantiÖed by qPCR and western blot. Hyperphosphorilated Tau was detected by immunohistochemistry.Results: TauKO and hTau mice were both severely impaired in motor coordination tasks. Dopamine levels were dramatically decreased in the striata of TauKO mice but partially rescued in hTau mice. hTau miceexpressed both 3R and 4R human Tau isoforms while wild-type mice only expressed 4RTau. However no hyperphosphorilated Tau accumulation was detected in the striatum nor in the SNpc of hTau mice. In additionthe number of DA neurons in the SNpc was not altered in the hTau group.Conclusions: Our results suggest that the lack of functional Tau or an abnormal Tau isoforms content affectmotor and cognitive behaviours. Severe motor phenotypes observed in the hTau group might be related to animbalance in Tau isoforms in the striatum.Thus, we propose the hTau mice as a suitable model to study molecular mechanisms underlying the pathological role of Tau in the basal ganglia.
Fil: Damianich, Ana. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina
Fil: Sartor, Manuela. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina
Fil: Espindola, Sonia Lorena. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina
Fil: Taravini, Irene Rita Eloisa. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Gershanik, Oscar Samuel. No especifíca;
Fil: Ferrario, Juan Esteban. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Avale, Maria Elena. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina
20th International Congress on Parkinson's Disease
Berlín
Alemania
International Parkinson and Movement Disorder Society
Materia
TAU
MOTOR COORDINATION
FRONTOTEMPORAL DEMENTIA
COVID-19
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:11336/135550
Acceder
id CONICETDig_995f1079a38d143a28a58625262179a4
oai_identifier_str oai:ri.conicet.gov.ar:11336/135550
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Tau dysfunction in the basal ganglia of a mouse model of tauopathy related to PSPDamianich, AnaSartor, ManuelaEspindola, Sonia LorenaTaravini, Irene Rita EloisaGershanik, Oscar SamuelFerrario, Juan EstebanAvale, Maria ElenaTAUMOTOR COORDINATIONFRONTOTEMPORAL DEMENTIACOVID-19https://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3Objective: Determine motor coordination and neurochemical phenotypes in the basal ganglia of mice lacking the Tau protein or expressing an abnormal content of Tau isoforms.Background: Microtubule-associated protein TAU is expressed in neurons and involved in microtubule polymerization and axonal transport. Tauopathies are neurodegenerative diseases, with presence of insoluble tau aggregates. Progressive Supranuclear Palsy (PSP) is a tauopathy that affects the basal ganglia thus leading PD symptoms. The pathological mechanisms of tauopathies have been extensively studied using animal models, mostly to analyze cognitive decline. Much less has been investigated about the role of normal and pathological Tau in the basal ganglia in those animal models. Here we investigated motor phenotypes and neurochemical changes in the striatum and substantia nigra pars compacta (SNpc) of mice lacking Tau (Tau KO) and in a mouse model of tauopathy (hTAU mice).Methods: We compared Wild type (WT), TauKO and hTAU mice in spontaneous locomotor activity in the open Öeld, motor coordination in the rotarod and cognitive performance in the novel object recognition task(NOR). Quantitation of dopaminergic (DA) neurons in the SNpc was done using stereology analysis.Dopamine and its metabolites were quantiÖed by HPLC. The relative amount of Tau isoforms was quantiÖed by qPCR and western blot. Hyperphosphorilated Tau was detected by immunohistochemistry.Results: TauKO and hTau mice were both severely impaired in motor coordination tasks. Dopamine levels were dramatically decreased in the striata of TauKO mice but partially rescued in hTau mice. hTau miceexpressed both 3R and 4R human Tau isoforms while wild-type mice only expressed 4RTau. However no hyperphosphorilated Tau accumulation was detected in the striatum nor in the SNpc of hTau mice. In additionthe number of DA neurons in the SNpc was not altered in the hTau group.Conclusions: Our results suggest that the lack of functional Tau or an abnormal Tau isoforms content affectmotor and cognitive behaviours. Severe motor phenotypes observed in the hTau group might be related to animbalance in Tau isoforms in the striatum.Thus, we propose the hTau mice as a suitable model to study molecular mechanisms underlying the pathological role of Tau in the basal ganglia.Fil: Damianich, Ana. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; ArgentinaFil: Sartor, Manuela. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; ArgentinaFil: Espindola, Sonia Lorena. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; ArgentinaFil: Taravini, Irene Rita Eloisa. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Gershanik, Oscar Samuel. No especifíca;Fil: Ferrario, Juan Esteban. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Avale, Maria Elena. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina20th International Congress on Parkinson's DiseaseBerlínAlemaniaInternational Parkinson and Movement Disorder SocietyInternational Parkinson and Movement Disorder Society2016info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/conferenceObjectCongresoJournalhttp://purl.org/coar/resource_type/c_5794info:ar-repo/semantics/documentoDeConferenciaapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/135550Tau dysfunction in the basal ganglia of a mouse model of tauopathy related to PSP; 20th International Congress on Parkinson's Disease; Berlín; Alemania; 2016; 1-11531-8257CONICET DigitalCONICETenghttps://www.mdsabstracts.org/sessions/parkinsonism-msa-psp-secondary-and-parkinsonism-plus-2016info:eu-repo/semantics/altIdentifier/url/https://movementdisorders.onlinelibrary.wiley.com/doi/10.1002/mds.26688Internacionalinfo:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T10:09:09Zoai:ri.conicet.gov.ar:11336/135550instacron: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 10:09:09.334CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Tau dysfunction in the basal ganglia of a mouse model of tauopathy related to PSP
title Tau dysfunction in the basal ganglia of a mouse model of tauopathy related to PSP
spellingShingle Tau dysfunction in the basal ganglia of a mouse model of tauopathy related to PSP
Damianich, Ana
TAU
MOTOR COORDINATION
FRONTOTEMPORAL DEMENTIA
COVID-19
title_short Tau dysfunction in the basal ganglia of a mouse model of tauopathy related to PSP
title_full Tau dysfunction in the basal ganglia of a mouse model of tauopathy related to PSP
title_fullStr Tau dysfunction in the basal ganglia of a mouse model of tauopathy related to PSP
title_full_unstemmed Tau dysfunction in the basal ganglia of a mouse model of tauopathy related to PSP
title_sort Tau dysfunction in the basal ganglia of a mouse model of tauopathy related to PSP
dc.creator.none.fl_str_mv Damianich, Ana
Sartor, Manuela
Espindola, Sonia Lorena
Taravini, Irene Rita Eloisa
Gershanik, Oscar Samuel
Ferrario, Juan Esteban
Avale, Maria Elena
author Damianich, Ana
author_facet Damianich, Ana
Sartor, Manuela
Espindola, Sonia Lorena
Taravini, Irene Rita Eloisa
Gershanik, Oscar Samuel
Ferrario, Juan Esteban
Avale, Maria Elena
author_role author
author2 Sartor, Manuela
Espindola, Sonia Lorena
Taravini, Irene Rita Eloisa
Gershanik, Oscar Samuel
Ferrario, Juan Esteban
Avale, Maria Elena
author2_role author
author
author
author
author
author
dc.subject.none.fl_str_mv TAU
MOTOR COORDINATION
FRONTOTEMPORAL DEMENTIA
COVID-19
topic TAU
MOTOR COORDINATION
FRONTOTEMPORAL DEMENTIA
COVID-19
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Objective: Determine motor coordination and neurochemical phenotypes in the basal ganglia of mice lacking the Tau protein or expressing an abnormal content of Tau isoforms.Background: Microtubule-associated protein TAU is expressed in neurons and involved in microtubule polymerization and axonal transport. Tauopathies are neurodegenerative diseases, with presence of insoluble tau aggregates. Progressive Supranuclear Palsy (PSP) is a tauopathy that affects the basal ganglia thus leading PD symptoms. The pathological mechanisms of tauopathies have been extensively studied using animal models, mostly to analyze cognitive decline. Much less has been investigated about the role of normal and pathological Tau in the basal ganglia in those animal models. Here we investigated motor phenotypes and neurochemical changes in the striatum and substantia nigra pars compacta (SNpc) of mice lacking Tau (Tau KO) and in a mouse model of tauopathy (hTAU mice).Methods: We compared Wild type (WT), TauKO and hTAU mice in spontaneous locomotor activity in the open Öeld, motor coordination in the rotarod and cognitive performance in the novel object recognition task(NOR). Quantitation of dopaminergic (DA) neurons in the SNpc was done using stereology analysis.Dopamine and its metabolites were quantiÖed by HPLC. The relative amount of Tau isoforms was quantiÖed by qPCR and western blot. Hyperphosphorilated Tau was detected by immunohistochemistry.Results: TauKO and hTau mice were both severely impaired in motor coordination tasks. Dopamine levels were dramatically decreased in the striata of TauKO mice but partially rescued in hTau mice. hTau miceexpressed both 3R and 4R human Tau isoforms while wild-type mice only expressed 4RTau. However no hyperphosphorilated Tau accumulation was detected in the striatum nor in the SNpc of hTau mice. In additionthe number of DA neurons in the SNpc was not altered in the hTau group.Conclusions: Our results suggest that the lack of functional Tau or an abnormal Tau isoforms content affectmotor and cognitive behaviours. Severe motor phenotypes observed in the hTau group might be related to animbalance in Tau isoforms in the striatum.Thus, we propose the hTau mice as a suitable model to study molecular mechanisms underlying the pathological role of Tau in the basal ganglia.
Fil: Damianich, Ana. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina
Fil: Sartor, Manuela. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina
Fil: Espindola, Sonia Lorena. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina
Fil: Taravini, Irene Rita Eloisa. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Gershanik, Oscar Samuel. No especifíca;
Fil: Ferrario, Juan Esteban. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Avale, Maria Elena. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina
20th International Congress on Parkinson's Disease
Berlín
Alemania
International Parkinson and Movement Disorder Society
description Objective: Determine motor coordination and neurochemical phenotypes in the basal ganglia of mice lacking the Tau protein or expressing an abnormal content of Tau isoforms.Background: Microtubule-associated protein TAU is expressed in neurons and involved in microtubule polymerization and axonal transport. Tauopathies are neurodegenerative diseases, with presence of insoluble tau aggregates. Progressive Supranuclear Palsy (PSP) is a tauopathy that affects the basal ganglia thus leading PD symptoms. The pathological mechanisms of tauopathies have been extensively studied using animal models, mostly to analyze cognitive decline. Much less has been investigated about the role of normal and pathological Tau in the basal ganglia in those animal models. Here we investigated motor phenotypes and neurochemical changes in the striatum and substantia nigra pars compacta (SNpc) of mice lacking Tau (Tau KO) and in a mouse model of tauopathy (hTAU mice).Methods: We compared Wild type (WT), TauKO and hTAU mice in spontaneous locomotor activity in the open Öeld, motor coordination in the rotarod and cognitive performance in the novel object recognition task(NOR). Quantitation of dopaminergic (DA) neurons in the SNpc was done using stereology analysis.Dopamine and its metabolites were quantiÖed by HPLC. The relative amount of Tau isoforms was quantiÖed by qPCR and western blot. Hyperphosphorilated Tau was detected by immunohistochemistry.Results: TauKO and hTau mice were both severely impaired in motor coordination tasks. Dopamine levels were dramatically decreased in the striata of TauKO mice but partially rescued in hTau mice. hTau miceexpressed both 3R and 4R human Tau isoforms while wild-type mice only expressed 4RTau. However no hyperphosphorilated Tau accumulation was detected in the striatum nor in the SNpc of hTau mice. In additionthe number of DA neurons in the SNpc was not altered in the hTau group.Conclusions: Our results suggest that the lack of functional Tau or an abnormal Tau isoforms content affectmotor and cognitive behaviours. Severe motor phenotypes observed in the hTau group might be related to animbalance in Tau isoforms in the striatum.Thus, we propose the hTau mice as a suitable model to study molecular mechanisms underlying the pathological role of Tau in the basal ganglia.
publishDate 2016
dc.date.none.fl_str_mv 2016
dc.type.none.fl_str_mv info:eu-repo/semantics/publishedVersion
info:eu-repo/semantics/conferenceObject
Congreso
Journal
http://purl.org/coar/resource_type/c_5794
info:ar-repo/semantics/documentoDeConferencia
status_str publishedVersion
format conferenceObject
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/135550
Tau dysfunction in the basal ganglia of a mouse model of tauopathy related to PSP; 20th International Congress on Parkinson's Disease; Berlín; Alemania; 2016; 1-1
1531-8257
CONICET Digital
CONICET
url http://hdl.handle.net/11336/135550
identifier_str_mv Tau dysfunction in the basal ganglia of a mouse model of tauopathy related to PSP; 20th International Congress on Parkinson's Disease; Berlín; Alemania; 2016; 1-1
1531-8257
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv https://www.mdsabstracts.org/sessions/parkinsonism-msa-psp-secondary-and-parkinsonism-plus-2016
info:eu-repo/semantics/altIdentifier/url/https://movementdisorders.onlinelibrary.wiley.com/doi/10.1002/mds.26688
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
application/pdf
dc.coverage.none.fl_str_mv Internacional
dc.publisher.none.fl_str_mv International Parkinson and Movement Disorder Society
publisher.none.fl_str_mv International Parkinson and Movement Disorder Society
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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