Impact of aging on the 6-OHDA-induced rat model of Parkinson’s disease
Autor(a) principal: | |
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Data de Publicação: | 2020 |
Outros Autores: | , , , , , , , |
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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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) instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação instacron:RCAAP |
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Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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