Gupta Daya S, Hubscher Charles H
Department of Anatomical Sciences and Neurobiology, University of Louisville Louisville, KY, USA.
Front Physiol. 2012 Feb 22;3:28. doi: 10.3389/fphys.2012.00028. eCollection 2012.
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.
在雄性和雌性动物中给予卵巢甾体雌激素雌二醇，已证实在多种实验模型中具有神经调节和神经保护作用。在本研究中，分析了T8严重慢性脊髓损伤（SCI）上方（T5 - T7水平）皮节的脊髓组织中前强啡肽原（PRDN）和磷酸化（丝氨酸369）κ-阿片受体（KOR - P）在17β雌二醇（EB）和安慰剂处理的成年雄性大鼠中的表达水平。选择强啡肽作为研究对象是因为：（1）先前已证明其在脊髓损伤后升高；（2）鞘内注射强啡肽会产生一些与脊髓损伤相同的不良反应；（3）已知其表达增加发生在多种不同的中枢神经性疼痛实验模型中。与未受伤的手术假手术对照组相比，安慰剂处理的脊髓损伤组在损伤水平以上的脊髓组织中，PRDN和KOR - P的细胞外水平显著升高，表明强啡肽水平增加。重要的是，EB处理的脊髓损伤组在损伤后6周未显示PRDN水平升高。对该水平组织的免疫组织化学分析表明，EB处理显著预防了脊髓损伤后PRDN与神经末梢标记物突触素I共标记的斑点表达增加。含强啡肽的终末与囊泡型谷氨酸受体2（谷氨酸能终末的标记物）共标记，这一发现与强啡肽不良反应的非阿片类基础一致。这些结果支持EB治疗在脊髓损伤后通过降低脊髓中过量的强啡肽水平发挥有益作用。通过操纵损伤后EB治疗的时间以及进行特定的功能评估的研究，将探讨这些有益作用是否归因于EB潜在的神经调节或神经保护作用。
