Suppression of neuroinflammation and immunomodulation by the acetylcholinesterase inhibitor rivastigmine.
In this study we determined the influence of cholinergic up-regulation by rivastigmine, an acetylcholinesterase inhibitor, on central nervous system inflammation. Neuroinflammation was induced in experimental autoimmune encephalomyelitis (EAE). Rivastigmine markedly ameliorated clinical symptoms of EAE and the spatial memory deficits induced by EAE. It also reduced demyelination, microglia activation and axonal damage. Rivastigmine decreased the reactivity of encephalitogenic T-cells and the production of pro-inflammatory cytokines (TNF-alpha, IFN-gamma and IL-17) without affecting IL-10 production. These effects were abolished by alpha7 nicotinic acetylcholine receptor antagonists. Antigen presentation was also affected by this treatment. Thus, rivastigmine treatment had immunomodulatory activity in EAE.
Nizri
Eran
E
Laboratory of Neuroimmunology, Department of Neurology, Agnes Ginges Center for Human Neurogenetics, Jerusalem, Israel.
Irony-Tur-Sinai
Michal
M
Faranesh
Nabil
N
Lavon
Iris
I
Lavi
Ehud
E
Weinstock
Marta
M
Brenner
Talma
T
D000818:Animals; D017951:Antigen Presentation / Q000187:drug effects; D002455:Cell Division / Q000276:immunology; D002800:Cholinesterase Inhibitors / Q000494:pharmacology*; D003072:Cognition Disorders / Q000188:drug therapy / Q000276:immunology / Q000473:pathology; D016207:Cytokines / Q000378:metabolism; D003711:Demyelinating Diseases / Q000188:drug therapy / Q000276:immunology; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000188:drug therapy* / Q000276:immunology* / Q000473:pathology; D005260:Female; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D018782:Maze Learning / Q000187:drug effects; D008568:Memory / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein / Q000276:immunology; D063308:Myelin-Oligodendrocyte Glycoprotein; D048448:Phenylcarbamates / Q000494:pharmacology*; D011978:Receptors, Nicotinic / Q000378:metabolism; D000068836:Rivastigmine; D013028:Space Perception / Q000187:drug effects; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D064569:alpha7 Nicotinic Acetylcholine Receptor
D002800:Cholinesterase Inhibitors; C579167:Chrna7 protein, human; C579166:Chrna7 protein, mouse; D016207:Cytokines; D007166:Immunosuppressive Agents; C571326:MOG protein, human; C571327:Mog protein, mouse; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein; D063308:Myelin-Oligodendrocyte Glycoprotein; D048448:Phenylcarbamates; D011978:Receptors, Nicotinic; D064569:alpha7 Nicotinic Acetylcholine Receptor; D000068836:Rivastigmine