Neuropeptide Y (NPY) intranasal delivery alleviates Machado-Joseph disease
Autor(a) principal: | |
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Data de Publicação: | 2021 |
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/10316/105448 https://doi.org/10.1038/s41598-021-82339-5 |
Resumo: | Machado-Joseph disease (MJD) is the most common dominantly-inherited ataxia worldwide with no effective treatment to prevent, stop or alleviate its progression. Neuropeptide Y (NPY) is a neuroprotective agent widely expressed in the mammalian brain. Our previous work showed that NPY overexpression mediated by stereotaxically-injected viral vectors mitigates motor deficits and neuropathology in MJD mouse models. To pursue a less invasive translational approach, we investigated whether intranasal administration of NPY would alleviate cerebellar neuropathology and motor and balance impairments in a severe MJD transgenic mouse model. For that, a NPY solution was administered into mice nostrils 5 days a week. Upon 8 weeks of treatment, we observed a mitigation of motor and balance impairments through the analysis of mice behavioral tests (rotarod, beam walking, pole and swimming tests). This was in line with a reduction of cerebellar pathology, evidenced by a preservation of cerebellar granular layer and of Purkinje cells and reduction of mutant ataxin-3 aggregate numbers. Furthermore, intranasal administration of NPY did not alter body weight gain, food intake, amount of body fat nor cholesterol or triglycerides levels. Our findings support the translational potential of intranasal infusion of NPY as a pharmacological intervention in MJD. |
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Neuropeptide Y (NPY) intranasal delivery alleviates Machado-Joseph diseaseAdministration, IntranasalAnimalsAtaxin-3CerebellumDisease Models, AnimalMachado-Joseph DiseaseMiceMice, TransgenicNeuropeptide YPurkinje CellsMachado-Joseph disease (MJD) is the most common dominantly-inherited ataxia worldwide with no effective treatment to prevent, stop or alleviate its progression. Neuropeptide Y (NPY) is a neuroprotective agent widely expressed in the mammalian brain. Our previous work showed that NPY overexpression mediated by stereotaxically-injected viral vectors mitigates motor deficits and neuropathology in MJD mouse models. To pursue a less invasive translational approach, we investigated whether intranasal administration of NPY would alleviate cerebellar neuropathology and motor and balance impairments in a severe MJD transgenic mouse model. For that, a NPY solution was administered into mice nostrils 5 days a week. Upon 8 weeks of treatment, we observed a mitigation of motor and balance impairments through the analysis of mice behavioral tests (rotarod, beam walking, pole and swimming tests). This was in line with a reduction of cerebellar pathology, evidenced by a preservation of cerebellar granular layer and of Purkinje cells and reduction of mutant ataxin-3 aggregate numbers. Furthermore, intranasal administration of NPY did not alter body weight gain, food intake, amount of body fat nor cholesterol or triglycerides levels. Our findings support the translational potential of intranasal infusion of NPY as a pharmacological intervention in MJD.Supported by the European Regional Development Fund through the Regional Operational Program Center 2020, Competitiveness Factors Operational Program (COMPETE 2020) and National Funds through Foundation for Science and Technology (FCT): UID/NEU/04539/2020, BrainHealth2020 projects (CENTRO-01-0145- FEDER-000008), ViraVector (CENTRO-01-0145-FEDER-022095), CortaCAGs (POCI-01-0145-FEDER-016719), SpreadSilencing POCI-01-0145-FEDER-029716, CancelStem (POCI-01-0145-FEDER-016390), and the SynSpread, European SCA3/MJD Initiative and ModelPolyQ under the EU Joint Program, the last two co-funded by the European Union H2020 program, GA No. 643417; by the National Ataxia Foundation, the American Portuguese Biomedical Research Fund and the Richard Chin and Lily Lock Machado–Joseph Disease Research Fund.Springer Nature2021-02-08info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articlehttp://hdl.handle.net/10316/105448http://hdl.handle.net/10316/105448https://doi.org/10.1038/s41598-021-82339-5eng2045-2322Duarte-Neves, JoanaCavadas, CláudiaAlmeida, Luís Pereira deinfo: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:RCAAP2023-04-06T10:20:06Zoai:estudogeral.uc.pt:10316/105448Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T21:22:01.257413Repositório 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 |
Neuropeptide Y (NPY) intranasal delivery alleviates Machado-Joseph disease |
title |
Neuropeptide Y (NPY) intranasal delivery alleviates Machado-Joseph disease |
spellingShingle |
Neuropeptide Y (NPY) intranasal delivery alleviates Machado-Joseph disease Duarte-Neves, Joana Administration, Intranasal Animals Ataxin-3 Cerebellum Disease Models, Animal Machado-Joseph Disease Mice Mice, Transgenic Neuropeptide Y Purkinje Cells |
title_short |
Neuropeptide Y (NPY) intranasal delivery alleviates Machado-Joseph disease |
title_full |
Neuropeptide Y (NPY) intranasal delivery alleviates Machado-Joseph disease |
title_fullStr |
Neuropeptide Y (NPY) intranasal delivery alleviates Machado-Joseph disease |
title_full_unstemmed |
Neuropeptide Y (NPY) intranasal delivery alleviates Machado-Joseph disease |
title_sort |
Neuropeptide Y (NPY) intranasal delivery alleviates Machado-Joseph disease |
author |
Duarte-Neves, Joana |
author_facet |
Duarte-Neves, Joana Cavadas, Cláudia Almeida, Luís Pereira de |
author_role |
author |
author2 |
Cavadas, Cláudia Almeida, Luís Pereira de |
author2_role |
author author |
dc.contributor.author.fl_str_mv |
Duarte-Neves, Joana Cavadas, Cláudia Almeida, Luís Pereira de |
dc.subject.por.fl_str_mv |
Administration, Intranasal Animals Ataxin-3 Cerebellum Disease Models, Animal Machado-Joseph Disease Mice Mice, Transgenic Neuropeptide Y Purkinje Cells |
topic |
Administration, Intranasal Animals Ataxin-3 Cerebellum Disease Models, Animal Machado-Joseph Disease Mice Mice, Transgenic Neuropeptide Y Purkinje Cells |
description |
Machado-Joseph disease (MJD) is the most common dominantly-inherited ataxia worldwide with no effective treatment to prevent, stop or alleviate its progression. Neuropeptide Y (NPY) is a neuroprotective agent widely expressed in the mammalian brain. Our previous work showed that NPY overexpression mediated by stereotaxically-injected viral vectors mitigates motor deficits and neuropathology in MJD mouse models. To pursue a less invasive translational approach, we investigated whether intranasal administration of NPY would alleviate cerebellar neuropathology and motor and balance impairments in a severe MJD transgenic mouse model. For that, a NPY solution was administered into mice nostrils 5 days a week. Upon 8 weeks of treatment, we observed a mitigation of motor and balance impairments through the analysis of mice behavioral tests (rotarod, beam walking, pole and swimming tests). This was in line with a reduction of cerebellar pathology, evidenced by a preservation of cerebellar granular layer and of Purkinje cells and reduction of mutant ataxin-3 aggregate numbers. Furthermore, intranasal administration of NPY did not alter body weight gain, food intake, amount of body fat nor cholesterol or triglycerides levels. Our findings support the translational potential of intranasal infusion of NPY as a pharmacological intervention in MJD. |
publishDate |
2021 |
dc.date.none.fl_str_mv |
2021-02-08 |
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/10316/105448 http://hdl.handle.net/10316/105448 https://doi.org/10.1038/s41598-021-82339-5 |
url |
http://hdl.handle.net/10316/105448 https://doi.org/10.1038/s41598-021-82339-5 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
2045-2322 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.publisher.none.fl_str_mv |
Springer Nature |
publisher.none.fl_str_mv |
Springer Nature |
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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RCAAP |
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RCAAP |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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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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