Abstract: Sirtuin 1 in Experimental Allergic Encephalomyelitis (The 27th Annual Meeting of the CMSC and the 5th Cooperative Meeting of the CMSC-ACTRIMS)

Saturday, June 1, 2013

Vamshi Nimmagadda, M.B.B.S. , Neurology, University of Maryland School of Medicine, Baltimore, MD

Tapas K Makar, Ph.D. , Neurology, University of Maryland School of Medicine, Baltimore, MD

James W Russell, M.D. , Neurology, University of Maryland School of Medicine, Baltimore, MD

Krish Chandrasekaran, Ph.D. , Neurology, University of Maryland School of Medicine, Baltimore, MD

David Trisler, Ph.D. , Neurology, University of Maryland School of Medicine, Baltimore, MD

Susan I Judge, Ph.D. , VA MS Center of Excellence - East, VA Maryland Health Care System, Baltimore, MD

Naveen K Nagalla, MBBS , Neurology, University of Maryland School of Medicine, Baltimore, MD

Christopher T Bever Jr., M.D., M.B.A. , Neurology, University of Maryland School of Medicine, Baltimore, MD

Background: Sirtuin 1 (SIRT1), also known as NAD-dependent deacetylase sirtuin -1, is a class III histone deacetylase which regulates the expression of proteins that contribute to stress responses and longevity. In some conditions it appears to exert a neuroprotective effect. In previous studies we showed that in experimental allergic encephalomyelitis (EAE), SIRT1 levels were increased in brain and spinal cord (Makar et al J Neurimmunol 2012; 252: 1).

Objectives: The aim of this study was to examine the effects of SIRT1 on EAE severity using a transgenic SIRT1 overexpressing mouse.

Methods: EAE was induced in wild type and SIRT1 overexpressing C57Bl/6J mice with oligodendroglial glycoprotein peptide (MOG35-55) using previously reported methods (ref above). Mice were examined, scored clinically and brains and spinal cords examined immunohistochemically.

Results: Clinical severity was reduced in the overexpressing mice compared to wild type and this correlated with reduced demyelination, less axonal loss and a reduction in inflammatory infiltration. Fewer apoptotic cells were found in the tissue of SIRT1 overexpressing mice.

Conclusions: These results are consistent with a neuroprotective effect of SIRT1 in EAE but further studies will be required to determine whether the reduction in severity is an indirect effect of SIRT1 in the overexpressing mouse.

P38 Sirtuin 1 in Experimental Allergic Encephalomyelitis