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研究生:簡玉筑
研究生(外文):Yu-ChuChien
論文名稱:多巴胺損傷程度對於陣發式磁波刺激誘發的長期增益可塑性在帕金森氏症大鼠上之影響
論文名稱(外文):Severity-Dependent Effects of Dopamine Depletion on LTP-like Plasticity after Theta Burst Stimulation in Parkinsonian Rats
指導教授:陳家進陳家進引用關係
指導教授(外文):Jia-Jing Chen
學位類別:碩士
校院名稱:國立成功大學
系所名稱:生物醫學工程學系
學門:生命科學學門
學類:生物化學學類
論文種類:學術論文
論文出版年:2012
畢業學年度:100
語文別:英文
論文頁數:33
中文關鍵詞:長期增益帕金森氏症可塑性經顱磁刺激陣發式磁波刺激
外文關鍵詞:long-term potentiationParkinson’s diseasePlasticitytranscranial magnetic stimulation (TMS)Theta burst stimulation (TBS)
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一種新式重複經顱磁刺激:陣發式磁波刺激(TBS),已被證實能夠有效調節運動皮質可塑性,對於帕金森氏症有治療潛力。然而,TBS所引發大腦興奮性之長期增益可塑性在帕金森氏症病人上還是具有爭議。為了避免臨床上的變異、長期藥物治療效應以及病人不同嚴重程度的影響,本研究使用人體的TBS方法應用在半邊6-OHDA誘發帕金森氏症的大鼠模型。為了量測間歇性陣發磁波刺激(iTBS)模式在帕金森氏症大鼠的皮質可塑性,首先我們確認不同模式的TBS在正常大鼠麻醉下的動作誘發電位(MEP)改變。我們將27隻大鼠平均地分配成控制組、iTBS600模式組、cTBS600模式組,進而觀察皮質興奮性對時間的改變。此外,我們也將帕金森氏症大鼠對於iTBS引發的皮質可塑性和多巴胺損傷程度做相關性分析。我們分別使用患病初期(6-OHDA誘發後一周)和慢性(6-OHDA誘發後四周)帕金森氏症大鼠來執行與正常大鼠相同的iTBS實驗流程來觀察其長期塑性。並且評估藥物誘發的旋轉行為測試和多巴胺細胞損傷程度。在不同TBS模式對於正常大鼠的實驗中,我們的結果發現cTBS使得MEP降低近10分鐘而iTBS促使MEP上升長達30分(p 〈 0.05)。在帕金森氏症大鼠中,iTBS在急性大鼠有比較少MEP上升而在慢性大鼠的MEP沒有改變,表示比較嚴重的大鼠缺乏長期塑性。更進一步的探討發現,iTBS誘發MEP改變和旋轉測試以及多巴胺損傷程度具有很大的相關性。最後,從我們的研究可結論出多巴胺損傷程度對我們的帕金森氏症大鼠模型的長期塑性有很大的影響。這些結果也許在建立新式治療策略上有很大幫助,例如使用TBS對帕金森氏症初期症患者做早期介入治療。
A specific type of repetitive transcranial magnetic stimulation (rTMS), theta burst stimulation (TBS), has been proven to be able to effectively modulate motor cortical plasticity which might have therapeutic potential for Parkinson’s disease (PD). However, the induction of long-term potentiation (LTP)-like motor cortex plasticity followed TBS in PD is still controversial. To avoid clinical heterogeneity, pharmacological effects, and different severity of the disease, we adopted human iTBS methods to the hemiparkinsonian rat model induced by injection of 6-hydroxydopamine. To measure the changes of cortical plasticity in PD rat model after iTBS, we first confirmed the 30-min changes of motor evoked potentials (MEPs) of anesthetized normal rats after varied TBS protocols. Twenty-seven normal rats were equally assigned to sham control, intermittent TBS 600 (iTBS) and continuous TBS 600 (cTBS) group for observing the time course changes of cortical excitability. Furthermore, we examined the possible correlation between iTBS-induced cortical plasticity and the severity of dopamine depletion in PD rats. Nine young (post-lesion one week) and nine chronic (post-lesion over four weeks) PD rats were chosen to perform the same iTBS protocols to observe the LTP-like plasticity at these stages of PD progression. The apomorphine-induced rotation behavior and dopaminergic neurons degeneration level were evaluated. For normal rats under varied TBS protocols, our results indicated that the cTBS reduced MEPs for 10 mins in comparison with the increased MEP amplitudes 5 min after iTBS and remained enhanced for up to 30 min (p 〈 0.05). In contrast, less facilitated MEP pattern in young PD rats and no changed in MEP of chronic PD rats after iTBS were found, indicating the lack of iTBS-induced LTP-like plasticity in more severe PD rats. Furthermore, the changes in MEP amplitudes induced by iTBS were significantly correlated to the level of dopaminergic cell loss and rotational behavior in PD rats. We conclude that the severity of dopamine depletion is critically involved for expression of LTP-like plasticity in animal models of PD. These results might be useful for establishing the new therapeutic strategies, such as the early intervention of TBS treatment in PD subjects.
Contents
摘要 I
Abstract II
致謝 IV
Contents V
List of Figures VII
Chapter 1 Introduction 1
1.1 Introduction of Parkinson’s disease and therapeutic methods 1
1.2 Repetitive transcranial magnetic stimulation 2
1.3 Theta burst stimulation 4
1.4 Cortical excitability and TMS techniques 4
1.5 PD animal models 5
1.6 Motivation and the aims of this study 6
Chapter 2 Materials and Methods 8
2.1 Animal preparation 8
2.2 Parkinsonian rat model 8
2.3 Electrophysiological assessment of cortical excitability 9
2.4 TBS protocols 11
2.5 Behavior test 12
2.6 Histology 13
2.7 Experimental Design 14
2.8 Statistical analysis 15
Chapter 3 Results 17
3.1 Effect of various TBS schemes on LTP or LTD-like plasticity 17
3.2 Effect of iTBS in PD rats 20
3.2.1 Severity of PD rats in dopamine depletion 23
3.2.2 Correlation between cortical excitability and dopamine depletion 25
Chapter 4 Discussion and Conclusion 27
References 30


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