金鱼受到外伤性应激后的神经病理变化及其干预治疗

发布时间：2018-06-03 23:10

本文选题：外伤性损伤 + 5-HT_(2a)受体　；参考：《浙江大学》2010年硕士论文

【摘要】： 金鱼(Carassius auratus),现今作为一种模式生物已经被广泛应用于神经生理领域的结构与功能研究。然而,用金鱼建立损伤模型,其外伤性损伤与行为学的关系,以及损伤是否会引起特定脑区某些神经递质发生神经病理性变化,依然鲜有文献报道。本实验旨在探讨外伤性应激对金鱼造成的关于平衡和运动的神经病理性影响。建立金鱼剪鳍的外伤性损伤模型后,我们对金鱼的行为学状况进行定量,发现5-HT_(2a)受体表达量在术后小脑区域显著增加,在这种简单的脊椎动物中,证实了5-羟色胺能系统与行为控制之间存在关联。同时,在剪鳍金鱼中发现有显著的伴随caspase-8增加的细胞凋亡加剧现象,可能会对金鱼应激后的自我调节机制提供新的线索,提示自我修复过程可能涉及细胞凋亡途径。另外,我们也观察到术后金鱼的c-fos蛋白表达升高。总的来说,这些结果表明剪鳍的确能够诱导行为学水平和神经病理上的变化,说明金鱼可以作为一种研究体系来探讨创伤后应激的潜在机制,而且这种创伤模型进一步优化建立成PTSD模型也是可行的。此外,为了评估中枢系统药物是否可以在创伤性损伤后发挥神经保护作用,以及其可能的作用机制,我们分别对术后金鱼给予doxepin和SSRI治疗,通过检测与损伤相关的5-羟色胺能和凋亡等指标,以观察其是否会对该模型产生神经保护作用。研究发现,5-HT_(2a)受体的下调和5-HT_(2c)受体的上调,BAD蛋白水平也下降,但是C-fos蛋白水平没有变化,显示创伤模型的行为学及神经病理变化可以同过CNS药物得以部分改善,而这主要基于5-羟色胺能以及细胞凋亡进程的调节。然而,对doxepin以及SSRI治疗作用的深入研究有待继续,尤其是在行为学水平。
[Abstract]:Carassius auratus, which is now widely used as a model organism, has been widely used in the study of structure and function in the field of neurophysiology. However, the use of goldfish to establish the damage model, the relationship between the traumatic injury and the behavioral science, and the neuropathic changes of certain neurotransmitters in the specific brain region, is still Xian Youwen This experiment aims to explore the neuropathic effects of traumatic stress on balance and movement caused by goldfish. After establishing a traumatic injury model of goldfish fins, we quantified the behavioral status of goldfish, and found that the expression of 5-HT_ (2a) receptor was significantly increased in the cerebellum region after the operation, in this simple vertebrate. The relationship between 5- serotonin energy system and behavioral control was confirmed. At the same time, there was a significant increase in apoptosis associated with caspase-8 in the fin goldfish, which may provide new clues to the self-regulation mechanism of the goldfish stress, suggesting that the process of self repair may involve the apoptosis pathway. In addition, we also view the apoptosis pathway. The expression of c-fos protein in goldfish was increased after the operation. In general, these results suggest that the fins can indeed induce behavioral and neuropathological changes. It shows that goldfish can be used as a research system to explore the potential mechanism of post-traumatic stress, and the further optimization of this model to establish a PTSD model is also feasible.
In addition, in order to assess whether central nervous system drugs can play a neuroprotective role after traumatic injury and its possible mechanisms of action, doxepin and SSRI were given to the goldfish after the operation, and the 5- hydroxytryptamine and apoptosis related to damage were detected to observe whether it would produce neuroprotective effects on the model. The study found that the down regulation of the 5-HT_ (2a) receptor and the up regulation of the 5-HT_ (2C) receptor and the BAD protein level also decreased, but the C-fos protein level did not change, indicating that the behavioral and neuropathological changes in the traumatic model could be partially improved with the CNS drug, which was mainly based on the regulation of 5- serotonin and the process of apoptosis. However, do Further studies on the role of xepin and SSRI remain to be continued, especially at the behavioral level.
【学位授予单位】：浙江大学
【学位级别】：硕士
【学位授予年份】：2010
【分类号】：R741;R-332

【共引文献】