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.
Keywords: optic neuritis, multiple sclerosis, EAE, resveratrol, SIRT1, neuroprotection
Citation: Fonseca-Kelly Z, Nassrallah M, Uribe J, Khan RS, Dine K, Dutt M and Shindler KS (2012) Resveratrol neuroprotection in a chronic mouse model of multiple sclerosis. Front. Neur. 3:84. doi: 10.3389/fneur.2012.00084
Received: 19 March 2012; Accepted: 28 April 2012;
Published online: 24 May 2012.
Edited by:Hana Leiba, Kaplan Medical Center, Israel
Reviewed by:Patrick Yu Wai Man, Institute of Human Genetics – Newcastle University, UK
Copyright: © 2012 Fonseca-Kelly, Nassrallah, Uribe, Khan, Dine, Dutt and Shindler. 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.
*Correspondence: Kenneth S. Shindler, Department of Ophthalmology, F.M. Kirby Center for Molecular Ophthalmology, University of Pennsylvania Scheie Eye Institute, Stellar-Chance Laboratories, 3rd Floor, 422 Curie Blvd, Philadelphia, PA 19104, USA. e-mail: firstname.lastname@example.org
†Zoe Fonseca-Kelly and Mayssa Nassrallah have contributed equally to this work.