stilbenes and Demyelinating-Diseases

Treatment of experimental autoimmune encephalomyelitis (EAE) with resveratrol, an activator of sirtuin 1 (SIRT1), reduces disease severity. This suggested that activators of SIRT1, a highly conserved NAD-dependent protein deacetylase, might have immune-modulating or neuroprotective therapeutic effects in EAE. Previously, we showed that SIRT1 expression increases in EAE, suggesting that it is an adaptive response. In this study, we investigated the potential function of SIRT1 in regulating EAE using SIRT1-overexpressing mice. The current studies examine potential neuroprotective and immunomodulatory effects of SIRT1 overexpression in chronic EAE induced by immunization of C57BL/6 mice with myelin oligodendrocyte glycoprotein peptide 35-55. SIRT1 suppressed EAE clinical symptoms compared with wild-type EAE mice and prevented or altered the phenotype of inflammation in spinal cords; as a result, demyelination and axonal injury were reduced. Significant neuroprotective effects were observed, with fewer apoptotic cells found in the spinal cords of SIRT1-overexpressing EAE mice associated with increased brain-derived neurotrophic factor and NAD levels. Earlier, we showed that brain-derived neurotrophic factor and NAD play crucial neuroprotective roles in EAE. These results suggest that SIRT1 reduces neuronal loss in this chronic demyelinating disease model and that this is associated with a reduction in inflammation.

Topics: Animals; Apoptosis; Axons; Brain-Derived Neurotrophic Factor; Demyelinating Diseases; Encephalomyelitis, Autoimmune, Experimental; Female; Inflammation; Mice; Mice, Inbred C57BL; Myelin-Oligodendrocyte Glycoprotein; NAD; Neurons; Neuroprotective Agents; Resveratrol; Sirtuin 1; Spinal Cord; Stilbenes

Resveratrol is a phytoestrogen that has many beneficial actions. This study aimed to evaluate the effect of resveratrol on the complete blood count (CBC) and the acetylcholinesterase (AChE) activity of lymphocytes of ovariectomized rats experimentally demyelinated by ethidium bromide (EB). Forty adult female Wistar rats (60 days, 200-220 g) were divided randomly into five groups (n = 4) to evaluate the demyelination phase and five groups (n = 4) to evaluate the remyelination phase. In each phase, the groups consisted of sham rats-G1; ovariectomized rats, not demyelinated, treated only with vehicle (ethanol 25%)-G2; demyelinated ovariectomized rats treated only with vehicle-G3; ovariectomized rats, not demyelinated, treated with resveratrol-G4; and demyelinated ovariectomized rats treated with resveratrol-G5. Only during the remyelination phase, CBC showed a significant difference (p < 0.05) in the number of monocytes between G2 and G5 groups. In the demyelination phase, there was a significant decrease (p < 0.05) in the AChE activity in the G4 group, while the G5 group was statistically similar to the G1, G2 and G4 groups. In the remyelination phase, there were no significant differences in the AChE activity among the groups. The treatment for 7 days with resveratrol with or without the experimental demyelization with EB appears to influence the AChE activity of lymphocytes, without changing the number of these cells in the circulation. However, in the remyelination phase, there seems to be stabilization in its effect on the lymphocyte AChE activity.

Topics: Acetylcholinesterase; Animals; Anti-Inflammatory Agents, Non-Steroidal; Blood Cell Count; Demyelinating Diseases; Enzyme Inhibitors; Ethidium; Female; Lymphocytes; Ovariectomy; Rats; Rats, Wistar; Resveratrol; Stilbenes

Myelin is a multilayered glial cell membrane that forms segmented sheaths around large-caliber axons of both the central nervous system (CNS) and peripheral nervous system (PNS). Myelin covering insures rapid and efficient transmission of nerve impulses. Direct visual assessment of local changes of myelin content in vivo could greatly facilitate diagnosis and therapeutic treatments of myelin-related diseases. Current histologic probes for the visualization of myelin are based on antibodies or charged histochemical reagents that do not enter the brain. We have developed a series of chemical compounds including (E,E)-1,4-bis(4'-aminostyryl)-2-dimethoxy-benzene termed BDB and the subject of this report, which readily penetrates the blood-brain barrier and selectively binds to the myelin sheath in brain. BDB selectively stains intact myelinated regions in wild-type mouse brain, which allows for delineation of cuprizone-induced demyelinating lesions in mouse brain. BDB can be injected IV into the brain and selectively detect demyelinating lesions in cuprizone-treated mice in situ. These studies justified further investigation of BDB as a potential myelin-imaging probe to monitor myelin pathology in vivo.

Topics: Aniline Compounds; Animals; Blood-Brain Barrier; Brain; Cuprizone; Demyelinating Diseases; Female; Fluorescent Dyes; Mice; Mice, Inbred C57BL; Mice, Mutant Strains; Myelin Sheath; Permeability; Stilbenes