大鼠苍白球神经降压素的电生理学和行为学研究

发布时间：2018-04-20 18:14

本文选题：苍白球 + 神经降压素　；参考：《青岛大学》2007年硕士论文

【摘要】： 苍白球(globus pallidus，GP)是基底神经节间接环路的重要核团，在机体运动功能调节中起着重要的作用。神经降压素(neurotensin，NT)是由13个氨基酸组成的肽类物质。在中枢神经系统，神经降压素作为神经递质或神经调质发挥重要作用，并且与中枢神经系统疾病密切相关。在6-OHDA损毁的大鼠，全身给予一种可以穿过血脑屏障的神经降压素类似物，可以产生抗帕金森病效应。形态学研究证实，苍白球接受来自纹状体的神经降压素能纤维支配，并且表达有神经降压素1型和2型受体。目的：观察神经降压素对正常大鼠和帕金森病模型大鼠苍白球神经元放电频率的影响，以及神经降压素对清醒大鼠整体姿势行为的调节。方法：本实验采用三管微电极细胞外电生理记录以及清醒状态下核团给药等实验方法。结果：1．在正常大鼠苍白球记录到的49个神经元中，压力注射0.1mM神经降压素可以兴奋其中的24个神经元，加药前放电频率为10.28±1.48Hz，加药后放电频率为14.86±2.01Hz(P＜0.001)，放电频率平均增加47.41±4.43％。在浓度从0.001mM到1mM范围内，神经降压素对苍白球神经元放电频率的增加呈钟型的量效依赖关系。利用192IgG-saporin破坏苍白球胆碱能神经元后，在记录到的24个苍白球神经元中，0.1 mM神经降压素可以兴奋其中的9个神经元，放电频率平均增加36.67±7.29％，与正常对照组相比没有明显差异(P＞0.05)。2．神经降压素羧基末端片段，神经降压素(8-13)，可以产生与神经降压素相似的兴奋效应，3mM神经降压素(8-13)可使苍白球神经元放电频率平均增加60.3±8.96％(P＜0.001)。但是其氨基末端片段，神经降压素(1-8)，对苍白球神经元放电频率没有任何影响。3．苍白球神经元给予非选择性神经降压素受体拮抗剂SR142948A，或者选择性神经降压素1型受体拮抗剂SR48692，均可阻断神经降压素所致的兴奋效应。4．在6-OHDA帕金森病模型大鼠损毁侧苍白球记录到的20个神经元中，0.1 mM神经降压素可以兴奋其中的8个神经元，其放电频率平均增加38.09±5.32％。而在帕金森病模型大鼠损毁对侧苍白球记录到的17个神经元中，，0.1mM神经降压素可以兴奋其中的10个神经元，放电频率平均增加85.88±18.91％，较损毁侧的兴奋效应明显增加(P＜0.05)。5．进一步实验观察了苍白球神经降压素对大鼠姿势行为的影响。在腹腔注射氟哌啶醇的条件下，大鼠单侧苍白球微量注射神经降压素(0.1mM)可以引起明显的对侧肢体偏转行为，这种行为可以被SR48692所阻断。结论：电生理学和行为学研究结果揭示神经降压素通过激活神经降压素1型受体兴奋苍白球神经元。该结果为进一步探讨苍白球神经降压素在机体运动障碍性疾病发病中的作用提供了理论和实验依据。
[Abstract]:Globus pallidusus GP) is an important nucleus in the indirect loop of basal ganglia and plays an important role in the regulation of motor function. Neurotensin NT is a peptide of 13 amino acids. Neurotensin plays an important role as a neurotransmitter or neuromodulator in the central nervous system and is closely related to central nervous system diseases. In 6-OHDA damaged rats, systemic administration of a neurotensin analogue that crosses the blood-brain barrier produces an anti-Parkinson 's disease effect. Morphological studies showed that the globus pallidus was innervated by neurotensin fibers from the striatum and expressed neurotensin type 1 and type 2 receptors. Aim: to observe the effects of neurotensin on the discharge frequency of neurons in the globus pallidus of normal and Parkinson's disease rats and the regulation of neurotensin on the global postural behavior of conscious rats. Methods: three-tube microelectrode cells were used to record the external electrophysiology and to receive the drug in the conscious state. The result is 1: 1. Among the 49 neurons recorded in the globus pallidus of normal rats, 24 neurons were excited by pressure injection of 0.1mM neurotensin. The discharge frequency was 10.28 卤1.48 Hz before administration, and 14.86 卤2.01Hz(P < 0.001g after injection. The discharge frequency increased 47.41 卤4.43 on average. In the range of concentration from 0.001mM to 1mM, the increase of neurotensin on the discharge frequency of globus pallidus neurons was in a dose-dependent manner. After 192IgG-saporin was used to destroy the cholinergic neurons of the globus pallidus, 9 of the 24 neurons of the globus pallidus were excited by 0.1 mm neurotensin, and the discharge frequency increased by 36.67 卤7.29 on average. There was no significant difference compared with the normal control group (P > 0.05). The end segment of carboxyl group of neurotensin, neurotensin 8-13, which can produce an excitatory effect similar to that of neurotensin, can increase the discharge frequency of neurons in the globus pallidus by an average of 60.3 卤8.96 (P < 0.001). But its amino terminal segment, neurotensin 1-8, had no effect on the discharge frequency of neurons in the globus pallidus. The excitatory effect of neurotensin induced by neurotensin was blocked by either the non-selective neurotensin receptor antagonist SR142948A or the selective neurotensin 1 receptor antagonist SR48692. Among the 20 neurons recorded in the damaged globus pallidus of 6-OHDA Parkinson's disease model, 0. 1 mm neurotensin could excite 8 of them, and its discharge frequency increased by 38. 09 卤5. 32 on average. However, in the 17 neurons recorded in the contralateral globus pallidus of Parkinson's disease model, 0.1 mm neurotensin could excite 10 of the neurons, and the discharge frequency was increased by 85.88 卤18.91 on average, which was significantly higher than that in the damaged side (P < 0.05). The effects of globus pallidus neurotensin on postural behavior in rats were further investigated. Under the condition of intraperitoneal injection of haloperidol, microinjection of neurotensin (0.1 mm) into the unilateral globus pallidus could induce obvious contralateral limb deflection, which could be blocked by SR48692. Conclusion: the results of electrophysiological and behavioral studies indicate that neurotensin excites globus pallidus neurons by activating neurotensin 1 receptor. The results provide a theoretical and experimental basis for the further study of the role of globus pallidus neurotensin in the pathogenesis of dyskinesia.
【学位授予单位】：青岛大学
【学位级别】：硕士
【学位授予年份】：2007
【分类号】：R33

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