生物谷報(bào)道：近日瑞典卡羅林斯卡研究院一項(xiàng)研究顯示雌激素受體ER-β對(duì)疼痛反映的傳入以及脊髓中間神經(jīng)元的形態(tài)形成和維持起著重要作用,。
早期研究已經(jīng)揭示雌激素可與兩種受體ER-α和ER-β結(jié)合,，影響我們體驗(yàn)疼痛的感覺(jué)，在決定人感知疼痛的敏感程度上起著重要的作用,，但是背后的機(jī)制卻不清楚,。
新研究描述了脊髓上這兩個(gè)受體表達(dá)的結(jié)果，顯示在體驗(yàn)疼痛的過(guò)程中雌激素受體ER-β尤為重要,。ER-β對(duì)脊髓中攜帶信息到大腦的神經(jīng)纖維部分的發(fā)展起著重要的作用,。這些神經(jīng)在諸如決定人疼痛敏感度及通常對(duì)感覺(jué)的反應(yīng)等功能上都很重要，ER-β是胚胎發(fā)育期間占支配地位的雌激素受體,。研究還顯示缺乏ER-β的老鼠神經(jīng)細(xì)胞發(fā)展滯后,，ER-β對(duì)成年動(dòng)物脊髓中神經(jīng)細(xì)胞存活和疼痛及感情傳遞非常重要。
這項(xiàng)研究成果顯示刺激ER-β的物質(zhì)能夠減輕疼痛,，可能意味著新型止痛藥將要誕生。該成果已經(jīng)發(fā)表在美國(guó)科學(xué)期刊PNAS上,。
參考文獻(xiàn)：
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.
