Inflammatory Response Modulation by Vitamin C in an MPTP Mouse Model of Parkinson’s Disease

Vitamin C (Vit C) is anutrient present in many foods, particularly citrus fruits, green vegetables, tomatoes, and potatoes. Vit C is studied for its applications in the prevention and management of different pathologies, including neurodegenerative diseases. Neuroinflammation is a defense mechanism...

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Autores principales:	Francesco De Nuccio, Antonia Cianciulli, Chiara Porro, Marianna Kashyrina, Melania Ruggiero, Rosa Calvello, Alessandro Miraglia, Giuseppe Nicolardi, Dario Domenico Lofrumento, Maria Antonietta Panaro
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	vitamin C inflammasome Parkinson’s disease neuroinflammation neuroprotection Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/5665cd56a5a34a9ba9a821484c72dd75
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spelling	oai:doaj.org-article:5665cd56a5a34a9ba9a821484c72dd752021-11-25T16:47:32ZInflammatory Response Modulation by Vitamin C in an MPTP Mouse Model of Parkinson’s Disease10.3390/biology101111552079-7737https://doaj.org/article/5665cd56a5a34a9ba9a821484c72dd752021-11-01T00:00:00Zhttps://www.mdpi.com/2079-7737/10/11/1155https://doaj.org/toc/2079-7737Vitamin C (Vit C) is anutrient present in many foods, particularly citrus fruits, green vegetables, tomatoes, and potatoes. Vit C is studied for its applications in the prevention and management of different pathologies, including neurodegenerative diseases. Neuroinflammation is a defense mechanism activated by a stimulus or an insult that is aimed at the preservation of the brain by promoting tissue repair and removing cellular debris; however, persistent inflammatory responses are detrimental and may lead to the pathogenesis and progression of neurodegenerative diseases like Parkinson’s disease (PD) and Alzheimer’s disease. PD is one of the most common chronic progressive neurodegenerative disorders, and oxidative stress is one of the most important factors involved in its pathogenesis and progression.Due to this, research on antioxidant and anti-inflammatory compounds is an important target for counteracting neurodegenerative diseases, including PD. In the central nervous system, the presence of Vit C in the brain is higher than in other body districts, but why and how this occurs is still unknown. In this research, Vit C, with its anti-inflammatory and anti-oxidative properties, is studied to better understand its contribution to brain protection; in particular, we have investigated the neuroprotective effects of Vit C in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced animal model of PD and its role in the modulation of neuroinflammation. First, we observed that Vit C significantly decreased the MPTP-induced loss of tyrosine hydroxylase (TH)-positive dopaminergic neuronal cells in the substantia nigra, as well as microglial cell activation and astrogliosis. Furthermore, gait and spontaneous locomotor activity, evaluated by an automated treadmill and the Open Field test, respectively, were partially ameliorated by Vit C treatment in MPTP-intoxicated animals. In relation to neuroinflammation, results show that Vit C reduced the protein and mRNA expression of inflammatory cytokines such as IL-6, TLR4, TNF-α, iNOS, and CD40, while anti-inflammatory proteins such as IL-10, CD163, TGF-β, and IL-4 increased. Interestingly, we show for the first time that Vit C reduces neuroinflammation by modulating microglial polarization and astrocyte activation. Moreover, Vit C was able to reduce NLRP3 activation, which is linked to the pathogenesis of many inflammatory diseases, including neuroinflammatory disorders. In conclusion, our study provides evidence that Vit C may represent a new promising dietary supplement for the prevention and alleviation of the inflammatory cascade of PD, thus contributing to neuroprotection.Francesco De NuccioAntonia CianciulliChiara PorroMarianna KashyrinaMelania RuggieroRosa CalvelloAlessandro MiragliaGiuseppe NicolardiDario Domenico LofrumentoMaria Antonietta PanaroMDPI AGarticlevitamin CinflammasomeParkinson’s diseaseneuroinflammationneuroprotectionBiology (General)QH301-705.5ENBiology, Vol 10, Iss 1155, p 1155 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	vitamin C inflammasome Parkinson’s disease neuroinflammation neuroprotection Biology (General) QH301-705.5
spellingShingle	vitamin C inflammasome Parkinson’s disease neuroinflammation neuroprotection Biology (General) QH301-705.5 Francesco De Nuccio Antonia Cianciulli Chiara Porro Marianna Kashyrina Melania Ruggiero Rosa Calvello Alessandro Miraglia Giuseppe Nicolardi Dario Domenico Lofrumento Maria Antonietta Panaro Inflammatory Response Modulation by Vitamin C in an MPTP Mouse Model of Parkinson’s Disease
description	Vitamin C (Vit C) is anutrient present in many foods, particularly citrus fruits, green vegetables, tomatoes, and potatoes. Vit C is studied for its applications in the prevention and management of different pathologies, including neurodegenerative diseases. Neuroinflammation is a defense mechanism activated by a stimulus or an insult that is aimed at the preservation of the brain by promoting tissue repair and removing cellular debris; however, persistent inflammatory responses are detrimental and may lead to the pathogenesis and progression of neurodegenerative diseases like Parkinson’s disease (PD) and Alzheimer’s disease. PD is one of the most common chronic progressive neurodegenerative disorders, and oxidative stress is one of the most important factors involved in its pathogenesis and progression.Due to this, research on antioxidant and anti-inflammatory compounds is an important target for counteracting neurodegenerative diseases, including PD. In the central nervous system, the presence of Vit C in the brain is higher than in other body districts, but why and how this occurs is still unknown. In this research, Vit C, with its anti-inflammatory and anti-oxidative properties, is studied to better understand its contribution to brain protection; in particular, we have investigated the neuroprotective effects of Vit C in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced animal model of PD and its role in the modulation of neuroinflammation. First, we observed that Vit C significantly decreased the MPTP-induced loss of tyrosine hydroxylase (TH)-positive dopaminergic neuronal cells in the substantia nigra, as well as microglial cell activation and astrogliosis. Furthermore, gait and spontaneous locomotor activity, evaluated by an automated treadmill and the Open Field test, respectively, were partially ameliorated by Vit C treatment in MPTP-intoxicated animals. In relation to neuroinflammation, results show that Vit C reduced the protein and mRNA expression of inflammatory cytokines such as IL-6, TLR4, TNF-α, iNOS, and CD40, while anti-inflammatory proteins such as IL-10, CD163, TGF-β, and IL-4 increased. Interestingly, we show for the first time that Vit C reduces neuroinflammation by modulating microglial polarization and astrocyte activation. Moreover, Vit C was able to reduce NLRP3 activation, which is linked to the pathogenesis of many inflammatory diseases, including neuroinflammatory disorders. In conclusion, our study provides evidence that Vit C may represent a new promising dietary supplement for the prevention and alleviation of the inflammatory cascade of PD, thus contributing to neuroprotection.
format	article
author	Francesco De Nuccio Antonia Cianciulli Chiara Porro Marianna Kashyrina Melania Ruggiero Rosa Calvello Alessandro Miraglia Giuseppe Nicolardi Dario Domenico Lofrumento Maria Antonietta Panaro
author_facet	Francesco De Nuccio Antonia Cianciulli Chiara Porro Marianna Kashyrina Melania Ruggiero Rosa Calvello Alessandro Miraglia Giuseppe Nicolardi Dario Domenico Lofrumento Maria Antonietta Panaro
author_sort	Francesco De Nuccio
title	Inflammatory Response Modulation by Vitamin C in an MPTP Mouse Model of Parkinson’s Disease
title_short	Inflammatory Response Modulation by Vitamin C in an MPTP Mouse Model of Parkinson’s Disease
title_full	Inflammatory Response Modulation by Vitamin C in an MPTP Mouse Model of Parkinson’s Disease
title_fullStr	Inflammatory Response Modulation by Vitamin C in an MPTP Mouse Model of Parkinson’s Disease
title_full_unstemmed	Inflammatory Response Modulation by Vitamin C in an MPTP Mouse Model of Parkinson’s Disease
title_sort	inflammatory response modulation by vitamin c in an mptp mouse model of parkinson’s disease
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/5665cd56a5a34a9ba9a821484c72dd75
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Inflammatory Response Modulation by Vitamin C in an MPTP Mouse Model of Parkinson’s Disease

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