2017-08-012024-05-17https://scholars.lib.ntu.edu.tw/handle/123456789/672734摘要：過動性不⾃自主運動疾病是⼀一群除了正常⾃自主運動之外、︑､額外出現、︑､無法⾃自主控制的運動障礙症狀，其中以舞蹈症與肌張⼒力不全症最為典型，在病態⽣生理機轉上與動作困難不⾃自主運動疾病巴⾦金森症互相對應。︒｡過動性不⾃自主運動疾病的病態⽣生理機轉與⼤大腦基底核迴路的超直接路徑與間接路徑功能異常、︑､造成直接路徑過度作⽤用有關，⽽而超直接路徑與間接路徑功能皆與視丘下核有密切關聯，因此視丘下核在過動性不⾃自主運動疾病病態⽣生理機轉扮演重要⾓角⾊色。︒｡多巴胺缺乏的狀況下，視丘下核出現⼤大量叢集式放電，動物出現動作困難的巴⾦金森症，⽽而在多巴胺過多的狀況下，視丘下核叢集式放電減少，可能導致過動性不⾃自主運動的出現。︒｡視丘下核叢集式放電與其細胞膜電位及其上的T型鈣離⼦子通道有關，因此給予去極化電流時，亦可導致視丘下核叢集式放電減少，改善動物動作困難的巴⾦金森症，⽽而給予過極化電流時，可使得視丘下核叢集式放電增加，造成正常動物出現類似巴⾦金森症的運動障礙。︒｡本計劃利⽤用左多巴在巴⾦金森動物上造成過動性不⾃自主運動的模型，以及3-NP造成紋狀體退化誘發出現過動性不⾃自主運動的模型，來研究並且證明電流刺激調節視丘下核可以有效地治療過動性不⾃自主運動疾病，並藉此計劃的進⾏行找出最好的電流刺激⽅方式。︒｡進⼀一步⽐比較電流刺激視丘下核及蒼⽩白球內側核，改善不⾃自主運動疾病的效果。︒｡本研究計劃將會為⼤大腦電刺激治療過動性不⾃自主運動疾病找到最好的治療⽅方式，並為未來過動性不⾃自主運動疾病的治療發展奠定新的基⽯石。︒｡<br> Abstract: Hyperkinetic movement disorders are a group of motor abnormalities characterized by uncontrollableand unwanted movements, in addition to normal voluntary actions. Among these movements, chorea,ballism and dystonia are the most typical examples opposite against the hypokinetic parkinsonianmovement. During the hyperkinetic movement state, it is presumed that there is decreased activities ofboth hyperdirect and indirect pathways in cortical-basal ganglia circuit, causing out-of-proportion signalintensity in the direct pathway and resulting in uncontrollable and unwanted movements. Subthalamicnucleus (STN) possess important role in both hyperdirect and indirect pathways and is closely related tothe pathophysiology of hyperkinetic movement. Lacking of dopamine can cause significantly increasingSTN burst firing and hypokinetic movement. In contrast, excessive dopamine which often causeshyperkinetic movements, may be directly associated with decreasing burst firing in STN. The formationof burst firing in STN is determined by subthalamic membrane potential and T-type calcium channelactivity. Using negative polarity current can readily depolarize subthalamic neuronal membranepotentials and thus change STN firing pattern from burst to spike firing. Interestingly, giving positivepolarity current can cause hyperpolarization in subthalamic neuronal membrane and even induceparkinsonism-like behavior in normal animals. Modulation of STN firing pattern with injection ofdepolarizing or hyperpolarizing current into STN is a highly important concept in the treatment ofhypokinetic movement, and this concept can be applied to the treatment hyperkinetic movementdisorders. It is therefore imperative to re-consider appropriate rationale in selecting stimulationparameters of STN DBS for hyperkinetic movement disorders, including pulsatile or constant, negativeor positive polarity current stimulation. In this three-year project, we aim to prove the value of STN DBSin the treatment of hyperkinetic movement disorders and clarify the best stimulation method in thiscondition. Two different types of hyperkinetic animal models will be used, namely levodopa-inducedhyperkinetic model in parkinsonian rats and 3-nitropropionic acid-induced hyperkinetic model, to studyhyperkinetic behavior during either neurotransmitter-related and neurodegeneration-related cortical-basalganglia circuit derangement. We will study both behavioral and electrophysiological effect of differentSTN stimulation parameters for the hyperkinetic movemen. Furthermore, we will compare the effectbetween STN DBS and GPi DBS in these hyperkinetic animal models. This study will provide theimportant rationale for choosing the stimulation parameters of DBS for hyperkinetic movements and willlay the cornerstone of future treatment development.