Impact of aging on the 6-OHDA-induced rat model of Parkinson’s disease

Detalhes bibliográficos
Autor(a) principal: Barata-Antunes, Sandra
Data de Publicação: 2020
Outros Autores: Teixeira, Fábio G., Mendes-Pinheiro, Bárbara, Domingues, Ana V., Vilaça-Faria, Helena, Marote, Ana, Silva, Deolinda, Sousa, R. A., Salgado, A. J.
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
Texto Completo: http://hdl.handle.net/1822/65504
Resumo: Parkinson’s disease (PD) is the second most common age-related neurodegenerative disorder. The neurodegeneration leading to incapacitating motor abnormalities mainly occurs in the nigrostriatal pathway due to the loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc). Several animal models have been developed not only to better understand the mechanisms underlying neurodegeneration but also to test the potential of emerging disease-modifying therapies. However, despite aging being the main risk factor for developing idiopathic PD, most of the studies do not use aged animals. Therefore, this study aimed at assessing the effect of aging in the unilateral 6-hydroxydopamine (6-OHDA)-induced animal model of PD. For this, female young adult and aged rats received a unilateral injection of 6-OHDA into the medial forebrain bundle. Subsequently, the impact of aging on 6-OHDA-induced effects on animal welfare, motor performance, and nigrostriatal integrity were assessed. The results showed that aging had a negative impact on animal welfare after surgery. Furthermore, 6-OHDA-induced impairments on skilled motor function were significantly higher in aged rats when compared with their younger counterparts. Nigrostriatal histological analysis further revealed an increased 6-OHDA-induced dopaminergic cell loss in the SNpc of aged animals when compared to young animals. Overall, our results demonstrate a higher susceptibility of aged animals to 6-OHDA toxic insult.
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spelling Impact of aging on the 6-OHDA-induced rat model of Parkinson’s disease6-hydroxydopamineAgingAnimal modelNeurodegenerationParkinson’s diseaseCiências Médicas::Ciências da SaúdeScience & TechnologyParkinson’s disease (PD) is the second most common age-related neurodegenerative disorder. The neurodegeneration leading to incapacitating motor abnormalities mainly occurs in the nigrostriatal pathway due to the loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc). Several animal models have been developed not only to better understand the mechanisms underlying neurodegeneration but also to test the potential of emerging disease-modifying therapies. However, despite aging being the main risk factor for developing idiopathic PD, most of the studies do not use aged animals. Therefore, this study aimed at assessing the effect of aging in the unilateral 6-hydroxydopamine (6-OHDA)-induced animal model of PD. For this, female young adult and aged rats received a unilateral injection of 6-OHDA into the medial forebrain bundle. Subsequently, the impact of aging on 6-OHDA-induced effects on animal welfare, motor performance, and nigrostriatal integrity were assessed. The results showed that aging had a negative impact on animal welfare after surgery. Furthermore, 6-OHDA-induced impairments on skilled motor function were significantly higher in aged rats when compared with their younger counterparts. Nigrostriatal histological analysis further revealed an increased 6-OHDA-induced dopaminergic cell loss in the SNpc of aged animals when compared to young animals. Overall, our results demonstrate a higher susceptibility of aged animals to 6-OHDA toxic insult.This research was funded by Prémios Santa Casa Neurociências—Prize Mantero Belard for Neurodegenerative Diseases Research (MB-28-2019); Portuguese Foundation for Science and Technology [Ph.D. fellowship to S.B.-A. (PD/BDE/135568/2018), B.M.-P. (SFRH/BD/120124/2016), A.M. (PDE/BDE/113598/2015), and D.S. (PD/BDE/135567/2018)]. This work was also funded by FEDER, through the Competitiveness Internationalization Operational Programme (POCI), and by National funds, through the Foundation for Science and Technology (FCT), under the scope of the projects POCI-01-0145-FEDER-007038; POCI-01-0145-FEDER-029751 and POCI-01-0145-FEDER-032619. This article has also been developed under the scope of the project NORTE-01-0145-FEDER-000023, supported by the Northern Portugal Regional Operational Programme (NORTE 2020), under the Portugal 2020 Partnership Agreement, through the European Regional Development Fund (FEDER).Multidisciplinary Digital Publishing InstituteUniversidade do MinhoBarata-Antunes, SandraTeixeira, Fábio G.Mendes-Pinheiro, BárbaraDomingues, Ana V.Vilaça-Faria, HelenaMarote, AnaSilva, DeolindaSousa, R. A.Salgado, A. J.2020-05-142020-05-14T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/1822/65504engBarata-Antunes, S.; Teixeira, F.G.; Mendes-Pinheiro, B.; Domingues, A.V.; Vilaça-Faria, H.; Marote, A.; Silva, D.; Sousa, R.A.; Salgado, A.J. Impact of Aging on the 6-OHDA-Induced Rat Model of Parkinson’s Disease. Int. J. Mol. Sci. 2020, 21, 3459.1661-65961422-006710.3390/ijms2110345932422916https://www.mdpi.com/1422-0067/21/10/3459info:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2023-07-21T12:37:21Zoai:repositorium.sdum.uminho.pt:1822/65504Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T19:33:37.964796Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse
dc.title.none.fl_str_mv Impact of aging on the 6-OHDA-induced rat model of Parkinson’s disease
title Impact of aging on the 6-OHDA-induced rat model of Parkinson’s disease
spellingShingle Impact of aging on the 6-OHDA-induced rat model of Parkinson’s disease
Barata-Antunes, Sandra
6-hydroxydopamine
Aging
Animal model
Neurodegeneration
Parkinson’s disease
Ciências Médicas::Ciências da Saúde
Science & Technology
title_short Impact of aging on the 6-OHDA-induced rat model of Parkinson’s disease
title_full Impact of aging on the 6-OHDA-induced rat model of Parkinson’s disease
title_fullStr Impact of aging on the 6-OHDA-induced rat model of Parkinson’s disease
title_full_unstemmed Impact of aging on the 6-OHDA-induced rat model of Parkinson’s disease
title_sort Impact of aging on the 6-OHDA-induced rat model of Parkinson’s disease
author Barata-Antunes, Sandra
author_facet Barata-Antunes, Sandra
Teixeira, Fábio G.
Mendes-Pinheiro, Bárbara
Domingues, Ana V.
Vilaça-Faria, Helena
Marote, Ana
Silva, Deolinda
Sousa, R. A.
Salgado, A. J.
author_role author
author2 Teixeira, Fábio G.
Mendes-Pinheiro, Bárbara
Domingues, Ana V.
Vilaça-Faria, Helena
Marote, Ana
Silva, Deolinda
Sousa, R. A.
Salgado, A. J.
author2_role author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Universidade do Minho
dc.contributor.author.fl_str_mv Barata-Antunes, Sandra
Teixeira, Fábio G.
Mendes-Pinheiro, Bárbara
Domingues, Ana V.
Vilaça-Faria, Helena
Marote, Ana
Silva, Deolinda
Sousa, R. A.
Salgado, A. J.
dc.subject.por.fl_str_mv 6-hydroxydopamine
Aging
Animal model
Neurodegeneration
Parkinson’s disease
Ciências Médicas::Ciências da Saúde
Science & Technology
topic 6-hydroxydopamine
Aging
Animal model
Neurodegeneration
Parkinson’s disease
Ciências Médicas::Ciências da Saúde
Science & Technology
description Parkinson’s disease (PD) is the second most common age-related neurodegenerative disorder. The neurodegeneration leading to incapacitating motor abnormalities mainly occurs in the nigrostriatal pathway due to the loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc). Several animal models have been developed not only to better understand the mechanisms underlying neurodegeneration but also to test the potential of emerging disease-modifying therapies. However, despite aging being the main risk factor for developing idiopathic PD, most of the studies do not use aged animals. Therefore, this study aimed at assessing the effect of aging in the unilateral 6-hydroxydopamine (6-OHDA)-induced animal model of PD. For this, female young adult and aged rats received a unilateral injection of 6-OHDA into the medial forebrain bundle. Subsequently, the impact of aging on 6-OHDA-induced effects on animal welfare, motor performance, and nigrostriatal integrity were assessed. The results showed that aging had a negative impact on animal welfare after surgery. Furthermore, 6-OHDA-induced impairments on skilled motor function were significantly higher in aged rats when compared with their younger counterparts. Nigrostriatal histological analysis further revealed an increased 6-OHDA-induced dopaminergic cell loss in the SNpc of aged animals when compared to young animals. Overall, our results demonstrate a higher susceptibility of aged animals to 6-OHDA toxic insult.
publishDate 2020
dc.date.none.fl_str_mv 2020-05-14
2020-05-14T00:00:00Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
format article
status_str publishedVersion
dc.identifier.uri.fl_str_mv http://hdl.handle.net/1822/65504
url http://hdl.handle.net/1822/65504
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv Barata-Antunes, S.; Teixeira, F.G.; Mendes-Pinheiro, B.; Domingues, A.V.; Vilaça-Faria, H.; Marote, A.; Silva, D.; Sousa, R.A.; Salgado, A.J. Impact of Aging on the 6-OHDA-Induced Rat Model of Parkinson’s Disease. Int. J. Mol. Sci. 2020, 21, 3459.
1661-6596
1422-0067
10.3390/ijms21103459
32422916
https://www.mdpi.com/1422-0067/21/10/3459
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Multidisciplinary Digital Publishing Institute
publisher.none.fl_str_mv Multidisciplinary Digital Publishing Institute
dc.source.none.fl_str_mv reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
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reponame_str Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
collection Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
repository.name.fl_str_mv Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
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