發(fā)布時(shí)間：2018-06-21 18:29

  本文選題：帕金森病 + 動(dòng)作電位��； 參考：《山東師范大學(xué)》2016年碩士論文

【摘要】：帕金森病(Parkinson’s disease,PD)病變的主要部位在中腦黑質(zhì)和基底神經(jīng)節(jié)。在基底神經(jīng)節(jié)中,蒼白球外側(cè)部(globus pallidus external segment,GPe)是重要的中繼核團(tuán),蒼白球內(nèi)側(cè)部(globus pallidus internal segment,GPi)是主要的輸出核團(tuán)。研究目的:本研究旨在探究PD大鼠GPe、GPi電生理學(xué)特征的變化以及兩個(gè)核團(tuán)之間局部場(chǎng)電位(local field potential,LFP)相關(guān)性的變化,包括:1、對(duì)PD大鼠運(yùn)動(dòng)障礙進(jìn)行量化測(cè)評(píng)。2、探究PD大鼠在清醒靜止和連續(xù)運(yùn)動(dòng)兩種狀態(tài)下GPe、GPi動(dòng)作電位和LFP的變化。3、探究PD大鼠GPe與GPi之間LFP相關(guān)性的變化。研究方法:建立PD大鼠模型,通過(guò)大鼠腦立體定位手術(shù),將兩束電極陣列分別植入同一只PD大鼠GPe、GPi內(nèi),使用Plexon多通道信號(hào)采集系統(tǒng)采集PD大鼠在清醒靜止和連續(xù)運(yùn)動(dòng)兩種狀態(tài)下的動(dòng)作電位和LFP。將采集到的動(dòng)作電位導(dǎo)入Offline Sorter軟件進(jìn)行聚類(lèi)分析,使用Neuro Explorer軟件分析每類(lèi)神經(jīng)元放電率和放電模式的變化;將采集到的LFP導(dǎo)入Matlab,使用LFP Analysis Software 2009軟件分析每個(gè)核團(tuán)時(shí)頻、功率譜密度和頻段分布的變化,使用LFP Analysis Software 2009軟件和Chronux軟件分析兩個(gè)核團(tuán)之間LFP相關(guān)性的變化,包括交叉相關(guān)分析和一致性分析。研究結(jié)果:1、行為學(xué)量化測(cè)評(píng)結(jié)果PD大鼠運(yùn)動(dòng)障礙測(cè)評(píng)結(jié)果:與正常大鼠相比,PD大鼠在跑步機(jī)上的最長(zhǎng)運(yùn)動(dòng)時(shí)間(min)變短(20 r/min:18.00±2.74 vs 26.98±0.91,P=0.03;30 r/min:3.33±1.45 vs 26.67±0.71,P0.01),步頻(steps/min)降低(20 r/min:73.33±7.00 vs 95.50±4.94,P=0.04;30 r/min:76.33±7.41 vs110.33±7.58,P0.01),失誤次數(shù)(times)增多(9 r/min:1.50±0.55 vs 0.67±0.33,P=0.04;15 r/min:2.50±0.76 vs 0.83±0.48,P=0.04;20 r/min:7.50±0.76 vs 1.50±0.43,P0.01;30 r/min:10.00±0.00 vs 2.00±0.58,P0.01)。跑步機(jī)轉(zhuǎn)速篩選結(jié)果:在12 r/min時(shí),兩組大鼠不連續(xù)運(yùn)動(dòng)頻率均較低,適宜采集大鼠在連續(xù)運(yùn)動(dòng)狀態(tài)下的腦電信號(hào)。2、GPe動(dòng)作電位分析結(jié)果GPe根據(jù)放電率和放電模式分為伴隨暫停的高頻率放電(high frequency pausers,HFP)和伴隨爆發(fā)的低頻率放電(low frequency bursters,LFB)兩類(lèi)神經(jīng)元。在清醒靜止和連續(xù)運(yùn)動(dòng)兩種狀態(tài)下,與正常大鼠相比,PD大鼠HFP放電率(spikes/s)降低(靜止:11.89±0.98 vs18.63±1.50,P0.01;運(yùn)動(dòng):16.08±1.51 vs 23.25±1.27,P0.01),變異系數(shù)(coefficient of variation,CV)值增大(靜止:1.06±0.05 vs 0.72±0.04,P0.01;運(yùn)動(dòng):1.33±0.03 vs 1.00±0.03,P0.01);PD大鼠LFB放電率降低(靜止:6.11±0.39 vs 10.33±0.79,P0.01;運(yùn)動(dòng):10.18±0.51vs 13.15±0.66,P0.01),CV值增大(靜止:2.31±0.23 vs 1.54±0.08,P0.01;運(yùn)動(dòng):2.48±0.21vs 1.62±0.15,P0.01)。與清醒靜止?fàn)顟B(tài)相比,在連續(xù)運(yùn)動(dòng)狀態(tài)下,正常大鼠和PD大鼠HFP放電率升高(正常:23.25±1.27 vs 18.63±1.50,P=0.03;PD:16.08±1.51 vs 11.89±0.98,P=0.03),CV值增大(正常:1.00±0.03 vs 0.72±0.04,P0.01;PD:1.33±0.03 vs 1.06±0.05,P0.01);LFB放電率升高(正常:13.15±0.66 vs 10.33±0.79,P=0.01;PD:10.18±0.51 vs 6.11±0.39,P0.01)。3、GPi動(dòng)作電位分析結(jié)果GPi只有一類(lèi)神經(jīng)元。在清醒靜止和連續(xù)運(yùn)動(dòng)兩種狀態(tài)下,與正常大鼠相比,PD大鼠GPi放電率升高(靜止:27.05±1.66 vs 23.18±1.25,P0.01;運(yùn)動(dòng):29.93±0.68 vs 25.16±0.65,P0.01),CV值增大(靜止:1.04±0.08 vs 0.72±0.03,P0.01;運(yùn)動(dòng):1.12±0.04 vs 0.89±0.03,P0.01)。與清醒靜止?fàn)顟B(tài)相比,在連續(xù)運(yùn)動(dòng)狀態(tài)下,正常大鼠和PD大鼠GPi放電率升高(正常:25.16±0.65 vs 23.18±1.25,P=0.03;PD:29.93±0.68 vs 27.05±1.66,P0.01),CV值增大(正常:0.89±0.03 vs 0.72±0.03,P0.01;PD:1.12±0.04 vs 1.04±0.08,P=0.03)。4、PD大鼠GPe、GPi局部場(chǎng)電位分析結(jié)果在清醒靜止?fàn)顟B(tài)下,與正常大鼠相比,PD大鼠GPe、GPi的LFP在0.5~12 Hz頻段的能量占總能量(0.5~200 Hz頻段的能量)的百分比降低(GPe:59.27±3.28 vs 74.44±1.68,P0.01;GPi:67.99±1.60 vs 80.88±1.80,P0.01),在12~35 Hz頻段的能量占總能量的百分比升高(GPe:28.32±1.94 vs 18.74±1.54,P0.01;GPi:26.32±2.16 vs 11.45±1.07,P0.01)。在連續(xù)運(yùn)動(dòng)狀態(tài)下,與正常大鼠相比,PD大鼠GPe、GPi的LFP在0.5~12 Hz頻段的能量占總能量的百分比降低(GPe:66.76±1.83 vs 79.11±2.80,P0.01;GPi:62.69±1.79 vs 76.79±1.19,P0.01),在12~35 Hz頻段的能量占總能量的百分比升高(GPe:24.53±1.64 vs13.65±1.91,P0.01;GPi:27.15±1.51 vs 16.10±0.80,P0.01),在35~70 Hz頻段的能量占總能量的百分比升高(GPe:3.03±0.48 vs 1.07±0.46,P=0.04;GPi:4.77±0.65 vs 2.03±0.34,P0.01)。5、PD大鼠GPe與GPi之間LFP相關(guān)性分析結(jié)果與正常大鼠相比,PD大鼠GPe與GPi之間LFP在0.5~12 Hz和12~35 Hz頻段的最大交叉相關(guān)系數(shù)增大(0.5~12 Hz:0.81±0.02 vs 0.37±0.03,P0.01;12~35 Hz:0.81±0.03 vs0.43±0.07,P0.01),平均相位一致性值增大(0.5~12 Hz:0.69±0.03 vs 0.25±0.01,P0.01;12~35 Hz:0.73±0.04 vs 0.30±0.06,P0.01)。研究結(jié)論:行為學(xué)量化測(cè)評(píng)實(shí)驗(yàn)結(jié)果顯示,PD大鼠出現(xiàn)運(yùn)動(dòng)障礙,表現(xiàn)為運(yùn)動(dòng)協(xié)調(diào)性差,尤其對(duì)高轉(zhuǎn)速控制能力差;12 r/min適宜大鼠在跑步機(jī)上連續(xù)運(yùn)動(dòng)。電生理學(xué)實(shí)驗(yàn)結(jié)果顯示,PD大鼠GPe神經(jīng)元放電率降低,GPi神經(jīng)元放電率升高;二者CV值都增大,表明放電規(guī)則性降低,放電模式發(fā)生變化。PD大鼠GPe、GPi的LFP在0.5~12 Hz頻段的能量降低,在12~35 Hz頻段的能量升高。PD大鼠GPe與GPi之間LFP在0.5~12 Hz和12~35Hz頻段的同步性都增強(qiáng)。與此同時(shí),在連續(xù)運(yùn)動(dòng)狀態(tài)下,GPe和GPi神經(jīng)元放電率升高,CV值增大,提示GPe、GPi與運(yùn)動(dòng)相關(guān)。
[Abstract]:The main site of the disease of Parkinson's disease (Parkinson 's disease, PD) is in the mesencephalic substantia nigra and basal ganglia. In the basal ganglia, the lateral part of the globus pallidus (globus pallidus external segment, GPe) is an important relay nucleus. The main output nucleus is the medial part of the globus pallidus (globus pallidus internal). The purpose of this study was to explore the changes in the electrophysiological characteristics of GPe and GPi in PD rats and the changes in the correlation between the local field potential (local field potential, LFP) between the two nuclei, including: 1. The quantitative measurement of the dyskinesia of PD rats was carried out, and the GPe in the two states of awake and continuous movement of PD rats was explored. The change of LFP correlation between rat GPe and GPi. Research methods: establish a PD rat model. Through the stereotaxic operation of the rat brain, the two beam electrode arrays were implanted into the same PD rat GPe, GPi, and the Plexon multichannel signal acquisition system was used to collect the action potential and LFP. of PD rats in two states of sober rest and continuous motion. The action potential is introduced into Offline Sorter software for clustering analysis, and Neuro Explorer software is used to analyze the variation of discharge rate and discharge mode of each type of neuron; the collected LFP is introduced into Matlab, and LFP Analysis Software 2009 software is used to analyze the time frequency, power spectral density and frequency distribution of each nucleus, and LFP Analysis So. Ftware 2009 software and Chronux software analyzed the changes of LFP correlation between two nuclear groups, including cross correlation analysis and consistency analysis. Results: 1, the results of PD rats were measured by behavioral quantification: compared with normal rats, the longest movement time (min) on the treadmill of PD rats was shorter (20 r/min:18.00 + 2.74 VS). 26.98 + 0.91, P=0.03, 30 r/min:3.33 + 1.45 vs 26.67 + 0.71, P0.01), the step frequency (steps/min) decreased (20 r/min:73.33 + 7 vs 95.50 + 4.94, P=0.04; 30 r/min:76.33 + 7.41 vs110.33 +% 7.58, P0.01), and the number of turnovers (Times) increased S 1.50 + 0.43, P0.01, 30 r/min:10.00 + 0 vs 2 + 0.58, P0.01). The result of the treadmill speed screening: at 12 r/min, the discontinuous motion frequency of the two groups of rats is low. It is suitable to collect the electroencephalogram.2 of the rat in the continuous motion state, and the result of GPe action potential analysis is divided into the high frequency with the discharge rate and the discharge mode. The discharge (high frequency pausers, HFP) and the low frequency discharge (low frequency bursters, LFB) two types of neurons with the outburst. In two states of sober rest and continuous motion, the HFP discharge rate (spikes/s) of the PD rats is lower than that of the normal rats (11.89 + 0.98 vs18.63 1.50, 16.08 + 1.51 23.25 + 1.27.) The value of coefficient of variation (CV) increased (still: 1.06 + 0.05 vs 0.72 + 0.04, P0.01; movement: 1.33 + 0.03 vs 1 + 0.03, P0.01); LFB discharge rate of PD rats decreased (still: 6.11 + 0.39 vs 10.33 + 0.79, P0.01. S 1.62 + 0.15, P0.01). Compared with the state of sober rest, the rate of HFP discharge in normal rats and PD rats increased (normal: 23.25 + 1.27 vs 18.63 + 1.50, P=0.03; PD:16.08 + 1.51 vs 11.89 + 0.98, P=0.03), and CV value increased (1 + 0.03 vs 0.72 + 0.04, P0.01. Normal: 13.15 + 0.66 vs 10.33 + 0.79, P=0.01, PD:10.18 + 0.51 vs 6.11 + 0.39, P0.01).3, GPi action potential analysis showed that GPi had only one class of neurons. In two states of sober rest and continuous movement, the GPi discharge rate of PD rats increased (still: 27.05 + 1.66 vs 23.18 + 1.25, P0.01) P0.01), the value of CV increased (still: 1.04 + 0.08 vs 0.72 + 0.03, P0.01; movement: 1.12 + 0.04 vs 0.89 + 0.03, P0.01). The rate of GPi discharge in normal rats and PD rats increased (normal: 25.16 + 0.65 vs 23.18 + 1.25, P=0.03; PD:29.93 + 0.68 VS). Vs 0.72 + 0.03, P0.01; PD:1.12 + 0.04 vs 1.04 + 0.08, P=0.03).4, PD rat GPe, GPi local field potential analysis results in sober rest state, PD rat GPe, GPi's energy accounted for the percentage of total energy (3.28 74.44 + 1.68). 9 + 1.60 vs 80.88 + 1.80, P0.01), the percentage of energy in the 12~35 Hz band increased (GPe:28.32 1.94 vs 18.74 + 1.54, P0.01; GPi:26.32 + 2.16 vs 11.45 + 1.07, P0.01). 1.83 vs 79.11 + 2.80, P0.01, GPi:62.69 + 1.79 vs 76.79 + 1.19, P0.01), the percentage of energy in the 12~35 Hz band increased (GPe:24.53 + 1.64 vs13.65 + 1.91, P0.01; GPi:27.15 + 1.51 vs 16.10 + 0.80,). .65 vs 2.03 + 0.34, P0.01).5, LFP correlation analysis between GPe and GPi in PD rats compared with normal rats, the maximum cross correlation coefficient of GPe and GPi between GPe and GPi in PD rats increased. 5~12 Hz:0.69 + 0.03 vs 0.25 + 0.01, P0.01; 12~35 Hz:0.73 + 0.04 vs 0.30 + 0.06, P0.01). Conclusion: the experimental results of quantitative behavior test showed that the dyskinesia was poor in the PD rats, especially for high speed control, and 12 r/min was suitable for the rats on the treadmill. The discharge rate of GPe neurons in PD rats decreased and the discharge rate of GPi neurons increased, and the two CV values increased, indicating that the discharge rule was reduced, the discharge mode changed in.PD rats GPe, the energy of GPi LFP in the 0.5~12 Hz band was reduced, and the synchronicity of the energy increase between the 12~35 Hz frequency band and the frequency segment of the 12~35 Hz band was both. At the same time, in continuous motion, the firing rate of GPe and GPi neurons increased and CV increased, suggesting that GPe and GPi were related to exercise.
【學(xué)位授予單位】：山東師范大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2016
【分類(lèi)號(hào)】：R742.5

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