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Resveratrol Neuroprotection in a Chronic Mouse Model of Multiple Sclerosis

Resveratrol is a naturally occurring polyphenol that activates SIRT1, an NAD-dependent deacetylase. SRT501, a pharmaceutical formulation of resveratrol with enhanced systemic absorption, prevents neuronal loss without suppressing inflammation in mice with relapsing experimental autoimmune encephalom...

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Autores principales: Fonseca-Kelly, Zoe, Nassrallah, Mayssa, Uribe, Jorge, Khan, Reas S., Dine, Kimberly, Dutt, Mahasweta, Shindler, Kenneth S.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Research Foundation 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3359579/
https://www.ncbi.nlm.nih.gov/pubmed/22654783
http://dx.doi.org/10.3389/fneur.2012.00084
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author Fonseca-Kelly, Zoe
Nassrallah, Mayssa
Uribe, Jorge
Khan, Reas S.
Dine, Kimberly
Dutt, Mahasweta
Shindler, Kenneth S.
author_facet Fonseca-Kelly, Zoe
Nassrallah, Mayssa
Uribe, Jorge
Khan, Reas S.
Dine, Kimberly
Dutt, Mahasweta
Shindler, Kenneth S.
author_sort Fonseca-Kelly, Zoe
collection PubMed
description Resveratrol is a naturally occurring polyphenol that activates SIRT1, an NAD-dependent deacetylase. SRT501, a pharmaceutical formulation of resveratrol with enhanced systemic absorption, prevents neuronal loss without suppressing inflammation in mice with relapsing experimental autoimmune encephalomyelitis (EAE), a model of multiple sclerosis (MS). In contrast, resveratrol has been reported to suppress inflammation in chronic EAE, although neuroprotective effects were not evaluated. The current studies examine potential neuroprotective and immunomodulatory effects of resveratrol in chronic EAE induced by immunization with myelin oligodendroglial glycoprotein peptide in C57/Bl6 mice. Effects of two distinct formulations of resveratrol administered daily orally were compared. Resveratrol delayed the onset of EAE compared to vehicle-treated EAE mice, but did not prevent or alter the phenotype of inflammation in spinal cords or optic nerves. Significant neuroprotective effects were observed, with higher numbers of retinal ganglion cells found in eyes of resveratrol-treated EAE mice with optic nerve inflammation. Results demonstrate that resveratrol prevents neuronal loss in this chronic demyelinating disease model, similar to its effects in relapsing EAE. Differences in immunosuppression compared with prior studies suggest that immunomodulatory effects may be limited and may depend on specific immunization parameters or timing of treatment. Importantly, neuroprotective effects can occur without immunosuppression, suggesting a potential additive benefit of resveratrol in combination with anti-inflammatory therapies for MS.
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spelling pubmed-33595792012-05-31 Resveratrol Neuroprotection in a Chronic Mouse Model of Multiple Sclerosis Fonseca-Kelly, Zoe Nassrallah, Mayssa Uribe, Jorge Khan, Reas S. Dine, Kimberly Dutt, Mahasweta Shindler, Kenneth S. Front Neurol Neuroscience Resveratrol is a naturally occurring polyphenol that activates SIRT1, an NAD-dependent deacetylase. SRT501, a pharmaceutical formulation of resveratrol with enhanced systemic absorption, prevents neuronal loss without suppressing inflammation in mice with relapsing experimental autoimmune encephalomyelitis (EAE), a model of multiple sclerosis (MS). In contrast, resveratrol has been reported to suppress inflammation in chronic EAE, although neuroprotective effects were not evaluated. The current studies examine potential neuroprotective and immunomodulatory effects of resveratrol in chronic EAE induced by immunization with myelin oligodendroglial glycoprotein peptide in C57/Bl6 mice. Effects of two distinct formulations of resveratrol administered daily orally were compared. Resveratrol delayed the onset of EAE compared to vehicle-treated EAE mice, but did not prevent or alter the phenotype of inflammation in spinal cords or optic nerves. Significant neuroprotective effects were observed, with higher numbers of retinal ganglion cells found in eyes of resveratrol-treated EAE mice with optic nerve inflammation. Results demonstrate that resveratrol prevents neuronal loss in this chronic demyelinating disease model, similar to its effects in relapsing EAE. Differences in immunosuppression compared with prior studies suggest that immunomodulatory effects may be limited and may depend on specific immunization parameters or timing of treatment. Importantly, neuroprotective effects can occur without immunosuppression, suggesting a potential additive benefit of resveratrol in combination with anti-inflammatory therapies for MS. Frontiers Research Foundation 2012-05-24 /pmc/articles/PMC3359579/ /pubmed/22654783 http://dx.doi.org/10.3389/fneur.2012.00084 Text en Copyright © 2012 Fonseca-Kelly, Nassrallah, Uribe, Khan, Dine, Dutt and Shindler. http://www.frontiersin.org/licenseagreement This is an open-access article distributed under the terms of the Creative Commons Attribution Non Commercial License, which permits non-commercial use, distribution, and reproduction in other forums, provided the original authors and source are credited.
spellingShingle Neuroscience
Fonseca-Kelly, Zoe
Nassrallah, Mayssa
Uribe, Jorge
Khan, Reas S.
Dine, Kimberly
Dutt, Mahasweta
Shindler, Kenneth S.
Resveratrol Neuroprotection in a Chronic Mouse Model of Multiple Sclerosis
title Resveratrol Neuroprotection in a Chronic Mouse Model of Multiple Sclerosis
title_full Resveratrol Neuroprotection in a Chronic Mouse Model of Multiple Sclerosis
title_fullStr Resveratrol Neuroprotection in a Chronic Mouse Model of Multiple Sclerosis
title_full_unstemmed Resveratrol Neuroprotection in a Chronic Mouse Model of Multiple Sclerosis
title_short Resveratrol Neuroprotection in a Chronic Mouse Model of Multiple Sclerosis
title_sort resveratrol neuroprotection in a chronic mouse model of multiple sclerosis
topic Neuroscience
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3359579/
https://www.ncbi.nlm.nih.gov/pubmed/22654783
http://dx.doi.org/10.3389/fneur.2012.00084
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