选择性孕酮受体激动剂奈司酮对慢性实验性自身免疫性脑脊髓炎的疗效。
Efficacy of the selective progesterone receptor agonist Nestorone for chronic experimental autoimmune encephalomyelitis.
作者信息
Garay Laura, Gonzalez Deniselle Maria Claudia, Sitruk-Ware Regine, Guennoun Rachida, Schumacher Michael, De Nicola Alejandro F
机构信息
Laboratory of Neuroendocrine Biochemistry, Instituto de Biologia y Medicina Experimental, Buenos Aires, Argentina; Dept. of Human Biochemistry, Faculty of Medicine, University of Buenos Aires, Argentina.
Laboratory of Neuroendocrine Biochemistry, Instituto de Biologia y Medicina Experimental, Buenos Aires, Argentina; Dept. of Physiology, Faculty of Medicine, University of Buenos Aires, Argentina.
出版信息
J Neuroimmunol. 2014 Nov 15;276(1-2):89-97. doi: 10.1016/j.jneuroim.2014.08.619. Epub 2014 Aug 28.
Progesterone plays a protective role in the experimental autoimmune encephalomyelitis (EAE) model of multiple sclerosis (MS). Besides spinal cord neuropathology, MS patients present a dysfunctional hippocampus. In this work we studied the therapeutic effects of the progestin Nestorone in the brain of mice with chronic EAE. Nestorone decreased clinical grade and enhanced motor behavior. In addition, it increased cell proliferation and doublecortin positive neuroblasts in the hippocampus, increased GABAergic interneurons and attenuated the number of Iba1+ microglia/macrophages, events possibly linked to enhancement of neurogenesis. Therefore, Nestorone protected against hippocampus abnormalities and improved functional outcomes of EAE mice, suggesting its potential value for MS.
孕酮在多发性硬化症（MS）的实验性自身免疫性脑脊髓炎（EAE）模型中发挥保护作用。除脊髓神经病理学外，MS患者还存在海马功能障碍。在这项研究中，我们研究了孕激素奈司酮对慢性EAE小鼠大脑的治疗作用。奈司酮降低了临床分级并增强了运动行为。此外，它增加了海马中的细胞增殖和双皮质素阳性神经母细胞，增加了γ-氨基丁酸能中间神经元，并减少了Iba1 +小胶质细胞/巨噬细胞的数量，这些事件可能与神经发生的增强有关。因此，奈司酮可预防EAE小鼠的海马异常并改善其功能结局，提示其对MS的潜在价值。
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