Intranasal delivery of mitochondria for treatment of Parkinson’s Disease model rats lesioned with 6-hydroxydopamine

Abstract The feasibility of delivering mitochondria intranasally so as to bypass the blood–brain barrier in treating Parkinson's disease (PD), was evaluated in unilaterally 6-OHDA-lesioned rats. Intranasal infusion of allogeneic mitochondria conjugated with Pep-1 (P-Mito) or unconjugated (Mito)...

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Autores principales:	Jui-Chih Chang, Yi-Chun Chao, Huei-Shin Chang, Yu-Ling Wu, Hui-Ju Chang, Yong-Shiou Lin, Wen-Ling Cheng, Ta-Tsung Lin, Chin-San Liu
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/824287c98e7647ef93824da6b45e81ce
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spelling	oai:doaj.org-article:824287c98e7647ef93824da6b45e81ce2021-12-02T15:45:27ZIntranasal delivery of mitochondria for treatment of Parkinson’s Disease model rats lesioned with 6-hydroxydopamine10.1038/s41598-021-90094-w2045-2322https://doaj.org/article/824287c98e7647ef93824da6b45e81ce2021-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-90094-whttps://doaj.org/toc/2045-2322Abstract The feasibility of delivering mitochondria intranasally so as to bypass the blood–brain barrier in treating Parkinson's disease (PD), was evaluated in unilaterally 6-OHDA-lesioned rats. Intranasal infusion of allogeneic mitochondria conjugated with Pep-1 (P-Mito) or unconjugated (Mito) was performed once a week on the ipsilateral sides of lesioned brains for three months. A significant improvement of rotational and locomotor behaviors in PD rats was observed in both mitochondrial groups, compared to sham or Pep-1-only groups. Dopaminergic (DA) neuron survival and recovery > 60% occurred in lesions of the substantia nigra (SN) and striatum in Mito and P-Mito rats. The treatment effect was stronger in the P-Mito group than the Mito group, but the difference was insignificant. This recovery was associated with restoration of mitochondrial function and attenuation of oxidative damage in lesioned SN. Notably, P-Mito suppressed plasma levels of inflammatory cytokines. Mitochondria penetrated the accessory olfactory bulb and doublecortin-positive neurons of the rostral migratory stream (RMS) on the ipsilateral sides of lesions and were expressed in striatal, but not SN DA neurons, of both cerebral hemispheres, evidently via commissural fibers. This study shows promise for intranasal delivery of mitochondria, confirming mitochondrial internalization and migration via RMS neurons in the olfactory bulb for PD therapy.Jui-Chih ChangYi-Chun ChaoHuei-Shin ChangYu-Ling WuHui-Ju ChangYong-Shiou LinWen-Ling ChengTa-Tsung LinChin-San LiuNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-14 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Jui-Chih Chang Yi-Chun Chao Huei-Shin Chang Yu-Ling Wu Hui-Ju Chang Yong-Shiou Lin Wen-Ling Cheng Ta-Tsung Lin Chin-San Liu Intranasal delivery of mitochondria for treatment of Parkinson’s Disease model rats lesioned with 6-hydroxydopamine
description	Abstract The feasibility of delivering mitochondria intranasally so as to bypass the blood–brain barrier in treating Parkinson's disease (PD), was evaluated in unilaterally 6-OHDA-lesioned rats. Intranasal infusion of allogeneic mitochondria conjugated with Pep-1 (P-Mito) or unconjugated (Mito) was performed once a week on the ipsilateral sides of lesioned brains for three months. A significant improvement of rotational and locomotor behaviors in PD rats was observed in both mitochondrial groups, compared to sham or Pep-1-only groups. Dopaminergic (DA) neuron survival and recovery > 60% occurred in lesions of the substantia nigra (SN) and striatum in Mito and P-Mito rats. The treatment effect was stronger in the P-Mito group than the Mito group, but the difference was insignificant. This recovery was associated with restoration of mitochondrial function and attenuation of oxidative damage in lesioned SN. Notably, P-Mito suppressed plasma levels of inflammatory cytokines. Mitochondria penetrated the accessory olfactory bulb and doublecortin-positive neurons of the rostral migratory stream (RMS) on the ipsilateral sides of lesions and were expressed in striatal, but not SN DA neurons, of both cerebral hemispheres, evidently via commissural fibers. This study shows promise for intranasal delivery of mitochondria, confirming mitochondrial internalization and migration via RMS neurons in the olfactory bulb for PD therapy.
format	article
author	Jui-Chih Chang Yi-Chun Chao Huei-Shin Chang Yu-Ling Wu Hui-Ju Chang Yong-Shiou Lin Wen-Ling Cheng Ta-Tsung Lin Chin-San Liu
author_facet	Jui-Chih Chang Yi-Chun Chao Huei-Shin Chang Yu-Ling Wu Hui-Ju Chang Yong-Shiou Lin Wen-Ling Cheng Ta-Tsung Lin Chin-San Liu
author_sort	Jui-Chih Chang
title	Intranasal delivery of mitochondria for treatment of Parkinson’s Disease model rats lesioned with 6-hydroxydopamine
title_short	Intranasal delivery of mitochondria for treatment of Parkinson’s Disease model rats lesioned with 6-hydroxydopamine
title_full	Intranasal delivery of mitochondria for treatment of Parkinson’s Disease model rats lesioned with 6-hydroxydopamine
title_fullStr	Intranasal delivery of mitochondria for treatment of Parkinson’s Disease model rats lesioned with 6-hydroxydopamine
title_full_unstemmed	Intranasal delivery of mitochondria for treatment of Parkinson’s Disease model rats lesioned with 6-hydroxydopamine
title_sort	intranasal delivery of mitochondria for treatment of parkinson’s disease model rats lesioned with 6-hydroxydopamine
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/824287c98e7647ef93824da6b45e81ce
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Intranasal delivery of mitochondria for treatment of Parkinson’s Disease model rats lesioned with 6-hydroxydopamine

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