探討視丘下核的腦深層刺激術對 正常大鼠與巴金森氏模式鼠之腦區活化的影響

巴金森氏症（Parkinson’s disease）是一種常見的退化性神經疾病，患者大腦中的黑質區之多巴胺神經元退化甚至死亡，導致多巴胺大量減少，造成黑質-紋狀體之神經路徑的運動調節功能喪失。腦深層刺激術 (Deep Brain Stimulation, DBS) 目前廣泛的使用在晚期嚴重的巴金森氏症病人身上，大部分患者接受視丘下核的腦深層刺激術（STN-DBS）的治療後都可以有效控制自主運動，改善基本的生活品質。然而近期研究指出STN-DBS可能會造成非運動性的副作用，目前仍不清楚患者在進行STN-DBS的治療後有哪些腦區直接或間接的受到活化，因此本實驗借由對正常大鼠與巴金森氏症模式鼠進行連續四小時高頻的STN-DBS，利用c-Fos作為神經細胞活化的標定物，觀察DBS後那些腦區受到活化，同時也觀察DBS是否影響大鼠的行為。實驗結果顯示正常的大鼠在進行連續四小時的STN-DBS時，在行為上沒有顯著的影響。在130 Hz DBS組別中，STN-DBS不會造成正常大鼠的CPu、GP、MOTOR CORTEX、Hb、PVP和ZI腦區有顯著的活化，然而在1300 Hz DBS組別中，其腦區的神經細胞活化數目較多，而且在GP腦區還有神經細胞活化數目減少的趨勢。在巴金森氏症模式鼠的組別中，還沒接受130 Hz STN-DBS前CPu、GP、MOTOR CORTEX、Hb和PVP腦區已處在高活化的狀態，經過連續四小時130 Hz DBS後，可能可以抑制STN高度活化的狀態，導致CPu和GP對側腦區活性降低，MOTOR CORTEX兩側活性降低。因此我們可以推斷頻率可能是STN-DBS的重要參數。除此之外單邊的STN-DBS會造成兩側的腦區皆有細胞活性的改變，可能透過雙邊的調節來維持正常的生理功能。此外我們推測巴金森氏症模式鼠的腦部神經細胞具有較高的活性，STN-DBS可以抑制腦部的高活化狀態。

關鍵字

巴金森氏症；腦深層刺激術

並列摘要

Abstract Parkinson’s disease is a disabling movement disorder due to thedegeneration of substantia nigra pars compacta (SNc) dopamine neurons. DBS-STN (Deep Brain Stimulation Subthalamic Nucleus), which is thought to affect the pathological neuronal activity and abnormal oscillactions in the basal ganglia caused by the loss of dopamine in the nigrostriatal system, is now the most frequently practiced surgical therapy for treating PD patients. In the present study, we have successfully induced PD model rats for development an integrated electrophysiology instrument suitable for the DBS procedure. The major purpose of this study is to identify which brain regions would be activated after DBS-STN. In our studies, we used c-Fos immunostaining to label rat brain regions that were activated under different conditions. We found that the neuronal activity of subthalamic nucleus (STN), substantia nigra (SN), globus pallidus (GP), caudate putamen(CPu), motor cortex, habenular nucleus (Hb) and paraventricular thalamic nucleus posterior (PVP) were not affected by 130 Hz DBS, but the neuronal activity of these areas increased by 1300 Hz DBS in normal rats. The result indicated that the super high frequency would increase a wide range of neuronal activity of the brain. However, the PD rats’ neuronal activity of these areas was in hyperactive state before DBS. After 130 Hz DBS, the neuronal activity of CPu, GP, motor cortex would decrease but the neuronal activity increased in Hb and PVP. These results suggested that HFS-DBS would change the neuronal activity of GP, CPu, Motor cortex, Hb and PVP in the PD rats. It may be related to the alleviation of the amphetamine-induced rotation.

並列關鍵字

Parkinson' disease ； deep brain stimulation

參考文獻

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探討視丘下核的腦深層刺激術對正常大鼠與巴金森氏模式鼠之腦區活化的影響

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