Treatment with a component of red wine, resveratrol, in a virus-induced murine model for multiple sclerosis

Background: While axonal degeneration occurs in multiple sclerosis (MS) and the extent of axonal damage is correlated with clinical disability, there is no efficient treatment targeting axonal preservation. In Wallerian degeneration slow (WldS) mice, axonal degeneration is delayed due to an increased nicotinamide adenine dinucleotide (NAD) biosynthetic enzyme Nmnat activity. SIRT1 is the downstream effector of the increased Nmnat activity. Preservation of axons in WldS mice is beneficial in experimental autoimmune encephalomyelitis (EAE), an autoimmune model for MS. Resveratrol is a natural polyphenol compound of red wine used in human clinical trials to treat cancer and can cross the blood-brain barrier. Resveratrol can enhance SIRT1 activity, which confers axonal preservation, and exhibit anti-inflammatory and antiviral activities. Objective: To test whether resveratrol could be therapeutic, possibly by limiting axonal damage in a viral model for MS, Theiler's murine encephalomyelitis virus (TMEV) infection. Methods: Female SJL/J mice were infected with the DA strain of TMEV. Infected mice were fed a diet containing 0.04% resveratrol (20 mg/kg/day) during the acute stage of infection (days 0 to 14) or during the chronic stage (days 21 to 35), or a control diet. Results: Clinically, the mice treated during the acute stage showed more weight gain than control mice at 2 weeks postinfection (p < 0.001, by ANOVA). Central nervous system (CNS) tissues and spleen mononuclear cells were harvested 5 weeks after infection. The mice treated during the chronic stage tended to have higher clinical and pathological scores than control mice, although they did not reach statistical significance. There were no significant differences in viral persistence in the CNS or lymphoproliferative responses to the virus among groups. We speculate that the significant weight gain during the acute stage in the early resveratrol treatment group could be due to a neuroprotective property of resveratrol. Conclusions: Since degenerated axons do not regenerate in the CNS, axonal degeneration results in permanent clinical disability in MS. Thus, potential axonal sparing activity by resveratrol could be of great benefit.