Neuropeptide Y (NPY) intranasal delivery alleviates Machado–Joseph disease

Abstract 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 overexp...

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Autores principales:	Joana Duarte-Neves, Cláudia Cavadas, Luís Pereira de Almeida
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/5e8895de18654bcbb26bcfb30a822f35
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spelling	oai:doaj.org-article:5e8895de18654bcbb26bcfb30a822f352021-12-02T13:30:28ZNeuropeptide Y (NPY) intranasal delivery alleviates Machado–Joseph disease10.1038/s41598-021-82339-52045-2322https://doaj.org/article/5e8895de18654bcbb26bcfb30a822f352021-02-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-82339-5https://doaj.org/toc/2045-2322Abstract 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.Joana Duarte-NevesCláudia CavadasLuís Pereira de AlmeidaNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-9 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Joana Duarte-Neves Cláudia Cavadas Luís Pereira de Almeida Neuropeptide Y (NPY) intranasal delivery alleviates Machado–Joseph disease
description	Abstract 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.
format	article
author	Joana Duarte-Neves Cláudia Cavadas Luís Pereira de Almeida
author_facet	Joana Duarte-Neves Cláudia Cavadas Luís Pereira de Almeida
author_sort	Joana Duarte-Neves
title	Neuropeptide Y (NPY) intranasal delivery alleviates Machado–Joseph disease
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
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/5e8895de18654bcbb26bcfb30a822f35
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Neuropeptide Y (NPY) intranasal delivery alleviates Machado–Joseph disease

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