帕金森病异动症模型大鼠背外侧纹状体和黑质网状部θ振荡脑网络研究

发布时间：2018-01-24 20:36

本文关键词： 帕金森病左旋多巴异动症局部场电位　出处：《南方医科大学》2017年硕士论文　论文类型：学位论文

【摘要】：研究目的:左旋多巴诱导异动症(Levodopa induced dyskinesia,LID)是晚期帕金森病(Parkinson disease,PD)患者常见的致残性服药并发症,异动症发病机制目前尚未阐明。局部场电位记录(Local field potential,LFP)是研究PD及其运动并发症LID的电生理机制重要手段。目前尚缺乏利用局部场电位技术,记录LID大鼠基底节背外侧纹状体(dorsolateral striatum,dStr)和黑质网状部(substantia nigra pars reticulate,SNr)的振荡电活动并分析脑网络功能连接的研究。研究方法:将40只大鼠随机分成两组,经立体定向注射6-ODHDA偏侧造模(6-OHDAgroup,n=24)和等剂量生理盐水(Shamgroup,n=16),随后将两组大鼠随机分成两组,分别进行腹腔注射左旋多巴(L-DOPA)联合苄丝肼和等剂量生理盐水(saline)连续21天,每天一次。实验分为4组:6-OHDA+L-DOPA组,n=15;6-OHDA+saline 组,n=9;Sham+L-DOPA 组,n=8;Sham+saline 组,n=8,记录清醒、自由活动的4组大鼠每次打药后3小时内dStr和SNr局部场电位活动,分析功率谱密度(Power spectral density),相干性(coherence)和格兰杰因果分析(Granger causality analysis)。随后探讨5-HT自受体激动剂依托拉嗪(eltoprazine)对LID行为学以及电生理影响,将6-OHDA+L-DOPA组随机分成两组,6-OHDA+L-DOPA+Elto 组,n=9;6-OHDA+L-DOPA+saline 组,n=6,分析两组LID大鼠行为学和上述电生理变化。研究结果:相比于Sham+L-DOPA组,腹腔注射6-OHDA+L-DOPA组dStr和SNr的5-8Hz功率谱密度显著增强,二者5-8Hz相干性系数显著增强;相比与 Sham+saline 组,6-ODHA+saline 组 24-36Hz 功率谱密度增强,二者 24-36Hz相干性显著性增强;6-OHDA +L-DOPA组dStr和SNr增强的5-8Hz振荡电活动与L-DOPA注药后3小时内不同时间点的AIMs评分成正相关关系,与1-21天左旋多巴注药后AIMs评分未见相关性。6-OHDA+L-DOPA组中,SNr→dStr的5-8Hz格兰杰因果系数显著高于Sham+L-DOPA组;6-ODHA+saline组中,dStr→SNr的24-36Hz格兰杰因果系数显著高于Sham+saline组。腹腔注射5-HT自受体激动剂依托拉嗪(eltoprazine)显著降低6-OHDA+L-DOPA组AIMs评分、功率谱密度、相干性系数、格兰杰因果系数。研究结论:自由活动状态下LID大鼠SNr和dStr的θ频段(5-8Hz)振荡电活动显著增高,并且两部位θ振荡具有相干性。这种增高的θ频段振荡电活动与LID大鼠单次打药后3小时以内不同时间点的AIMs评分成正相关。增强的θ频段的电活动在SNr和dStr两部位之间信息流动的方向为SNr→dStr,增强的24-36Hz频段的电活动在SNr和dStr两部位之间信息流动的方向为dStr→SNr,提示在LID状态下,SNr的θ振荡电活动起主导作用,可能是θ振荡电活动的源头。相反,在PD状态下,dStr的β振荡电活动起主导作用。5-HT自受体激动剂依托拉嗪能够降低LID大鼠行为学评分,同时降低增强的5-8Hz频段振荡电活动,并且θ振荡电活动在SNr和dStr之间信息流动的方向也随之下降。说明5-HT系统不仅参与LID病例生理机制,同时可能是通过调节基底节θ振荡电活动改善LID非随意运动症状。
[Abstract]:Objective: Levodopa induced dyskinesia was induced by levodopa. Lidis is a common disabling complication in patients with advanced Parkinson disease (PD). The pathogenesis of dyskinesia has not been elucidated at present. Local field potential is recorded in local field potential. LFP is an important method to study the electrophysiological mechanism of PD and its motor complication LID. The dorsolateral striatum was recorded in the dorsolateral striatum of the basal ganglia of LID rats. D Strand and substantia nigra pars reticulate. Methods: forty rats were randomly divided into two groups. 6-OHDA group (6-OHDA group) and the same dose of normal saline were injected into the model by stereotactic injection of 6-ODHDA (6-OHDAgroupN) and the same dose of normal saline (ShamgroupN) 16). Then the rats in the two groups were randomly divided into two groups. The rats were given intraperitoneal injection of L-DOPA plus benzylhydrazine and saline for 21 days respectively. Once a day. The experiment was divided into 4 groups: 1: 6-OHDA-DOPA group (n = 15); 6-OHDA saline group; Sham L-DOPA group; In Sham saline group, the local field potentials of dStr and SNr were recorded within 3 hours after administration of dStr and SNr. Power spectral density was analyzed. Coherence and Granger causality analysis. Then we studied the 5-HT autoreceptor agonist etalazine. Effects of eltoprazine on LID behavior and electrophysiology. The 6-OHDA L-DOPA group was randomly divided into two groups: 6-OHDA L-DOPA Elto group. 6-OHDA L-DOPA saline group was used to analyze the behavioral and electrophysiological changes of LID rats in two groups. Results: compared with Sham L-DOPA group. In the 6-OHDA L-DOPA group, the 5-8Hz power spectral density of dStr and SNr was significantly increased, and the coherence coefficient of 5-8Hz was significantly enhanced in the 6-OHDA L-DOPA group. Compared with Sham saline group, the power spectral density of 6-ODHA saline group was increased, and the correlation between them was significantly enhanced. The 5-8Hz oscillatory activity enhanced by dStr and SNr in 6-OHDA L-DOPA group was positively correlated with the AIMs scores at different time points within 3 hours after L-DOPA injection. There was no correlation with the AIMs score of 1-21 days after L-DOPA injection. 6-OHDA L-DOPA group. 鈫扵he 5-8Hz Granger causality coefficient of dStr is significantly higher than that of Sham L-DOPA 6-ODHA saline. 鈫扵he 24-36Hz Granger causality coefficient of SNr was significantly higher than that of Sham saline. The AIMs score of 6-OHDA L-DOPA group was significantly decreased. Power spectral density, coherence coefficient, Granger causality coefficient. Conclusion: the oscillatory electrical activity of SNr and dStr in SNr and dStr in free activity state is significantly increased. This increased 胃 band oscillatory electrical activity was positively correlated with the AIMs score at different time points within 3 hours after single drug administration in LID rats. The direction of information flow between SNr and dStr is SNr. 鈫扗Str, enhanced 24-36Hz electrical activity between SNr and dStr flows in the direction of dStr. 鈫扴NR, which indicates that the 胃 oscillatory activity of SNR plays a leading role in the LID state, and may be the source of theta oscillatory activity. On the contrary, in PD state. The 尾 -oscillatory electrical activity of dStr plays a leading role. 5-HT self-receptor agonist etalazine can reduce the behavioral score of LID rats and decrease the enhanced oscillatory activity in 5-8Hz band. The direction of information flow between SNr and dStr also decreased, indicating that 5-HT system is not only involved in the physiological mechanism of LID cases. At the same time, it may be by regulating the basal ganglia 胃 oscillatory electrical activity to improve LID involuntary motion symptoms.
【学位授予单位】：南方医科大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R742.5;R-332

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