生物谷报道：近日瑞典卡罗林斯卡研究院一项研究显示雌激素受体ER-β对疼痛反映的传入以及脊髓中间神经元的形态形成和维持起着重要作用。
早期研究已经揭示雌激素可与两种受体ER-α和ER-β结合，影响我们体验疼痛的感觉，在决定人感知疼痛的敏感程度上起着重要的作用，但是背后的机制却不清楚。
新研究描述了脊髓上这两个受体表达的结果，显示在体验疼痛的过程中雌激素受体ER-β尤为重要。ER-β对脊髓中携带信息到大脑的神经纤维部分的发展起着重要的作用。这些神经在诸如决定人疼痛敏感度及通常对感觉的反应等功能上都很重要，ER-β是胚胎发育期间占支配地位的雌激素受体。研究还显示缺乏ER-β的老鼠神经细胞发展滞后，ER-β对成年动物脊髓中神经细胞存活和疼痛及感情传递非常重要。
这项研究成果显示刺激ER-β的物质能够减轻疼痛，可能意味着新型止痛药将要诞生。该成果已经发表在美国科学期刊PNAS上。
参考文献：
Published online before print September 4, 2007
Proc. Natl. Acad. Sci. USA, 10.1073/pnas.0703783104
Neuroscience
Differential neuroprotective and antiinflammatory effects of estrogen receptor (ER) and ER ligand treatment
( experimental autoimmune encephalomyelitis | neuroprotection | multiple sclerosis selective estrogen receptor modulators )
Seema Tiwari-Woodruff, Laurie Beth J. Morales, Ruri Lee, and Rhonda R. Voskuhl *
Multiple Sclerosis Program, Department of Neurology, David Geffen School of Medicine, University of California, Neuroscience Research Building 1, Room 475D, 635 Charles Young Drive South, Los Angeles, CA 90095
Edited by Bruce S. McEwen, The Rockefeller University, New York, NY, and approved July 31, 2007 (received for review April 24, 2007)
Treatment with either estradiol or an estrogen receptor (ER) ligand has been shown to be both antiinflammatory and neuroprotective in a variety of neurological disease models, but whether neuroprotective effects could be observed in the absence of an antiinflammatory effect has remained unknown. Here, we have contrasted effects of treatment with an ER vs. an ER ligand in experimental autoimmune encephalomyelitis, the multiple sclerosis model with a known pathogenic role for both inflammation and neurodegeneration. Clinically, ER ligand treatment abrogated disease at the onset and throughout the disease course. In contrast, ER ligand treatment had no effect at disease onset but promoted recovery during the chronic phase of the disease. ER ligand treatment was antiinflammatory in the systemic immune system, whereas ER ligand treatment was not. Also, ER ligand treatment reduced CNS inflammation, whereas ER ligand treatment did not. Interestingly, treatment with either the ER or the ER ligand was neuroprotective, as evidenced by reduced demyelination and preservation of axon numbers in white matter, as well as decreased neuronal abnormalities in gray matter. Thus, by using the ER selective ligand, we have dissociated the antiinflammatory effect from the neuroprotective effect of estrogen treatment and have shown that neuroprotective effects of estrogen treatment do not necessarily depend on antiinflammatory properties. Together, these findings suggest that ER ligand treatment should be explored as a potential neuroprotective strategy in multiple sclerosis and other neurodegenerative diseases, particularly because estrogen-related toxicities such as breast and uterine cancer are mediated through ER.
