Hainz Nadine, Becker Philipp, Rapp Daniel, Wagenpfeil Stefan, Wonnenberg Bodo, Beisswenger Christoph, Tschernig Thomas, Meier Carola
Institute of Anatomy and Cell Biology, Saarland University, Germany.
Institute for Medical Biometry, Epidemiology and Medical Informatics, Saarland University, Germany.
J Chem Neuroanat. 2017 Nov;85:21-26. doi: 10.1016/j.jchemneu.2017.06.003. Epub 2017 Jun 16.
Recent experiments showed that a pannexin-1 inhibitor, probenecid, reduced clinical symptoms in the murine experimental autoimmune encephalomyelitis when applied during the initial phase of neuronal inflammation. An inflammatory component is also present in a toxically induced inflammation and demyelination using cuprizone diet. Probenecid is a pannexin-1 antagonist and a probenecid therapy was investigated. Mice were fed for 10days with a cuprizone diet. In the following, the diet was continued but combined with a daily injection of a low dose of probenecid or solvent for 10days. Electron microscopy revealed demyelination in the optic nerve. The demyelination as measured by the axonal diameter was significantly reduced in the animals treated with 100mg per kg body weight probenecid. In comparison to controls, the number of leukocytes and lymphocytes in the peripheral blood was reduced in all cuprizone groups including the treatment group. In conclusion, early demyelination in the optic nerve was moderately reduced by 10days treatment with a low dose probenecid. This is a hint for the involvement of pannexin-1 modulated inflammation in cuprizone feeding induced toxic demyelination. Thus, probenecid is a candidate for the treatment of neuro-inflammation and multiple sclerosis.
近期实验表明，一种泛连接蛋白-1抑制剂丙磺舒，在神经元炎症初始阶段应用时，可减轻小鼠实验性自身免疫性脑脊髓炎的临床症状。在使用铜螯合剂饮食诱导的毒性炎症和脱髓鞘中也存在炎症成分。丙磺舒是一种泛连接蛋白-1拮抗剂，因此对丙磺舒治疗进行了研究。给小鼠喂食含铜螯合剂的饮食10天。随后，继续喂食该饮食，但同时每天注射低剂量丙磺舒或溶剂，持续10天。电子显微镜检查显示视神经存在脱髓鞘。用每千克体重100毫克丙磺舒治疗的动物，以轴突直径衡量的脱髓鞘程度显著降低。与对照组相比，包括治疗组在内的所有铜螯合剂组外周血中的白细胞和淋巴细胞数量均减少。总之，低剂量丙磺舒治疗10天可适度减轻视神经早期脱髓鞘。这提示泛连接蛋白-1调节的炎症参与了铜螯合剂喂养诱导的毒性脱髓鞘。因此，丙磺舒是治疗神经炎症和多发性硬化症的候选药物。
