Estradiol treatment prevents injury induced enhancement in spinal cord dynorphin expression.
Estradiol treatment prevents injury induced enhancement in spinal cord dynorphin expression.
复制标题
DOI：
10.3389/fphys.2012.00028
复制
发表时间：
2012
影响因子：
4
通讯作者：
Hubscher CH
中科院分区：
文献类型：
--
作者：
Gupta DS;Hubscher CH
在各种实验模型中，雌雄动物服用卵巢类固醇雌二醇已被证明具有神经调节和神经保护作用。在本研究中，我们用17κ雌二醇(EB)和安慰剂处理成年雄性大鼠，分析了T8严重慢性脊髓损伤(SCI)大鼠(T5-T7水平)的脊髓组织中前强啡肽(PRDN)和磷酸(丝氨酸369)β阿片受体(KOR-P)的表达水平。强啡肽之所以成为靶点，是因为(1)强啡肽先前被证明在脊髓损伤后升高，(2)鞘内注射强啡肽会产生与脊髓损伤相同的几种不良反应，(3)已知其表达增加发生在各种不同的中枢神经病理性疼痛实验模型中。与未损伤的手术假手术对照组相比，在脊髓损伤平面以上的脊髓组织中，安慰剂治疗组脊髓组织中PRDN和KOR-P的细胞外水平均显著升高，表明强啡肽水平增加。重要的是，EB治疗的脊髓损伤组在损伤后6 周没有显示出PRDN水平的升高。AT水平组织的免疫组织化学分析显示，EB治疗显著阻止了脊髓损伤后PRDN斑点共标记突触蛋白I的表达增加，突触蛋白I是一种神经末梢标志物。含有强啡肽的终末共同标记囊泡谷氨酸受体-2(谷氨酸能终末的标志)，这一发现与强啡肽不良反应的非阿片基础一致。这些结果支持EB通过减少脊髓中过量的强啡肽水平来治疗脊髓损伤后的有益作用。对损伤后EB治疗时机的研究以及特定的功能评估将解决EB的有益影响是由于EB潜在的神经调节作用还是神经保护作用。
Administration of the ovarian steroid estradiol in male and female animals has been shown to have neuromodulatory and neuroprotective effects in a variety of experimental models. In the present study, spinal tissues from dermatomes just above (T5–T7, at level) a severe chronic spinal cord injury (SCI) at T8 were analyzed for expression levels of prodynorphin (PRDN) and phospho-(serine 369) κ-opioid receptor (KOR-P) in 17 β estradiol (EB)- and placebo-treated adult male rats. Dynorphin was targeted since (1) it has previously been shown to be elevated post-SCI, (2) intrathecal injection of dynorphin produces several of the same adverse effects seen with a SCI, and (3) its increased expression is known to occur in a variety of different experimental models of central neuropathic pain. A significant elevation of extracellular levels of both PRDN and KOR-P in the placebo-treated SCI group relative to uninjured surgical sham controls was found in spinal tissues above the injury level, indicating increased dynorphin levels. Importantly, the EB-treated SCI group did not show elevations of PRDN levels at 6 weeks post-injury. Immunohistochemical analysis of at level tissues revealed that EB treatment significantly prevented a post-SCI increase in expression of PRDN puncta co-labeling synapsin I, a nerve terminal marker. The dynorphin-containing terminals co-labeled vesicular glutamate receptor-2 (a marker of glutamatergic terminals), a finding consistent with a non-opioid basis for the adverse effects of dynorphin. These results support a beneficial role for EB treatment post-SCI through a reduction in excessive spinal cord levels of dynorphin. Studies manipulating the timing of the EB treatment post-injury along with specific functional assessments will address whether the beneficial effects are due to EB’s potential neuromodulatory or neuroprotective action.
登录
查看更多内容
DOI：
10.1073/pnas.78.12.7783
发表时间：
1981-01-01
期刊：
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA-BIOLOGICAL SCIENCES
影响因子：
--
作者：
BOTTICELLI, LJ;COX, BM;GOLDSTEIN, A
通讯作者：
GOLDSTEIN, A
影响因子：
--
作者：
FADEN, AI;MOLINEAUX, CJ;COX, BM
通讯作者：
COX, BM
影响因子：
15.3
作者：
DIAMOND, B;YELTON, DE
通讯作者：
YELTON, DE
影响因子：
7.4
作者：
Carlton SM;Du J;Tan HY;Nesic O;Hargett GL;Bopp AC;Yamani A;Lin Q;Willis WD;Hulsebosch CE
通讯作者：
Hulsebosch CE
DOI：
10.1523/jneurosci.0763-09.2009
发表时间：
2009-07-22
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Gottsch ML;Navarro VM;Zhao Z;Glidewell-Kenney C;Weiss J;Jameson JL;Clifton DK;Levine JE;Steiner RA
通讯作者：
Steiner RA