Probenecid Application Prevents Clinical Symptoms and Inflammation in Experimental Autoimmune Encephalomyelitis.
Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system. Neurological impairments are caused by axonal damage due to demyelination and neuroinflammation within the central nervous system. T cells mediate the neuroinflammation. The activation of T cells is induced by the release of adenosine triphosphate and involves purinergic receptors as well as pannexin (Panx) proteins. As Panx1 is expressed on T cells, we here propose that application of probenecid, a known Panx inhibitor, will prevent the onset of clinical symptoms in a mouse model of MS, the experimental autoimmune encephalomyelitis (EAE) model. EAE-induced mice received daily injections of probenecid. Disease scores, T cell numbers, and microglia activation were compared between experimental groups. Probenecid treatment resulted in lower disease scores as compared to EAE animals. Probenecid-treated animals also displayed fewer inflammatory lesions. Microglia activation was not altered by treatment. In conclusion, probenecid prevented the onset of EAE.
Department of Anatomy and Cell Biology, Saarland University, Building 61, 66421, Homburg, Saar, Germany.
Nadine
N
Hainz
Department of Anatomy and Cell Biology, Saarland University, Building 61, 66421, Homburg, Saar, Germany.
Sandra
S
Wolf
Department of Anatomy and Cell Biology, Saarland University, Building 61, 66421, Homburg, Saar, Germany.
Thomas
T
Tschernig
Department of Anatomy and Cell Biology, Saarland University, Building 61, 66421, Homburg, Saar, Germany. Carola.Meier@uks.eu.
Carola
C
Meier
D000277:Adjuvants, Pharmaceutic / Q000627:therapeutic use*; D000818:Animals; D002490:Central Nervous System / Q000276:immunology / Q000473:pathology; D017630:Connexins / Q000037:antagonists & inhibitors*; D004195:Disease Models, Animal; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000188:drug therapy* / Q000276:immunology / Q000517:prevention & control; D005260:Female; D007249:Inflammation / Q000188:drug therapy / Q000517:prevention & control*; D008213:Lymphocyte Activation / Q000276:immunology; D018655:Lymphocyte Count; D051379:Mice; D008810:Mice, Inbred C57BL; D017628:Microglia / Q000276:immunology; D009103:Multiple Sclerosis / Q000276:immunology; D009419:Nerve Tissue Proteins / Q000037:antagonists & inhibitors*; D011339:Probenecid / Q000627:therapeutic use*
D000277:Adjuvants, Pharmaceutic; D017630:Connexins; D009419:Nerve Tissue Proteins; C503631:Panx1 protein, mouse; D011339:Probenecid
multiple sclerosis; neuroinflammation; pannexin; probenecid