暑假華藝文章4-以大鼠模式探討帕金森症患者睡眠失常之機轉
文章名稱:以大鼠模式探討帕金森症患者睡眠失常之機轉 The sleep Disturbance in Rats with Parkinsonism
作者名稱:呂瑾瑜 , 碩士 指導教授：張芳嘉
資料來源:無
內容摘要:帕金森氏症 (Parkinson’s Disease, PD) 於1817年由英國的帕金森醫師發表的病例報告之後，世人開始注意到這些患者。在許多人投入帕金森的研究之後，針對帕金森症患者的大腦進行種種實驗，發現患者腦中紋狀體 (striatum) 的多巴胺含量顯著少於正常人，進一步分析則發現，多巴胺減少是由於患者黑質 (substantia nigra, SN) 所存活分泌多巴胺的神經元大量減少，並由此結果得知帕金森患者所出現的眾多症狀皆起因於此。
本研究關心的重點在帕金森患者所產生的睡眠症狀上，這個部分較不為一般人所重視，有許多症狀產生的機轉仍待研究人員進一步了解。我們試著將藥物直接施打於大鼠大腦黑質處，阻斷黑質附近ubiquitin-proteasome system之功能，造成被ubiquitin結合的蛋白質無法經由proteasome分解而大量堆積於位在黑質的多巴胺神經元，而使微膠細胞 (microglia cell) 活化，造成多巴胺神經活性衰退，大鼠上產生類似PD患者的睡眠障礙症狀，並藉由此模式來探討PD患者睡眠產生改變的機轉是否經過微膠細胞活化所釋放之細胞素 (cytoki...
For patients with the Parkinson’s disease (PD), the degeneration of dopaminergic neurons causes the decrease of dopamine release from the substantia nigra pars compecta (SNpc) to the striatum. It is also found that the PD patient’s brain has inclusion bodies of α-synuclein in this area. These inclusion bodies can lead to activate mitochondrial and to subsequently release cytokines, such as tumor necrosis factor – alpha (TNF-α) and interlukin-1beta (IL-1β), which affect the PD patient’s sleep. We herein used a proteasome inhibitor, MG-132, to inhibit the function of proteasome, which caused the loss of dopaminergic neurons in SNpc, and subsequently changed the sleep architecture in rats. The total amount of NREMS was significantly increased, and the of wakefulness was decreased during the dark-period at the 7th day after MG-132 treatment. We administered tumor necrosis factor receptor fragment (TNFRF) and interlukin-1 receptor antagonist (IL-1ra), to elucidate the involvement of TNF-α and IL-1β in MG-132-induced sleep alteration. The MG-132-induced sleep alteration was reversed after...
參考文獻:
1.1. Parkinson J. An essay on the shaking palsy. 1817. J Neuropsychiatry Clin Neurosci 2002;14(2):223-36.
連結：
2.3. Poewe W. Non-motor symptoms in Parkinson's disease. Eur J Neurol 2008;15 Suppl 1:14-20.
連結：
3.4. Ziemssen T, Reichmann H. Non-motor dysfunction in Parkinson's disease. Parkinsonism Relat Disord 2007;13(6):323-32.
連結：
4.6. Kageyama H, Takenoya F, Hori Y, Yoshida T, Shioda S. Morphological interaction between galanin-like peptide- and dopamine-containing neurons in the rat arcuate nucleus. Regul Pept 2008;145(1-3):165-8.
連結：
5.7. Frank MJ. Dynamic dopamine modulation in the basal ganglia: a neurocomputational account of cognitive deficits in medicated and nonmedicated Parkinsonism. J Cogn Neurosci 2005;17(1):51-72.
作者名稱:呂瑾瑜 , 碩士 指導教授：張芳嘉
資料來源:無
內容摘要:帕金森氏症 (Parkinson’s Disease, PD) 於1817年由英國的帕金森醫師發表的病例報告之後，世人開始注意到這些患者。在許多人投入帕金森的研究之後，針對帕金森症患者的大腦進行種種實驗，發現患者腦中紋狀體 (striatum) 的多巴胺含量顯著少於正常人，進一步分析則發現，多巴胺減少是由於患者黑質 (substantia nigra, SN) 所存活分泌多巴胺的神經元大量減少，並由此結果得知帕金森患者所出現的眾多症狀皆起因於此。
本研究關心的重點在帕金森患者所產生的睡眠症狀上，這個部分較不為一般人所重視，有許多症狀產生的機轉仍待研究人員進一步了解。我們試著將藥物直接施打於大鼠大腦黑質處，阻斷黑質附近ubiquitin-proteasome system之功能，造成被ubiquitin結合的蛋白質無法經由proteasome分解而大量堆積於位在黑質的多巴胺神經元，而使微膠細胞 (microglia cell) 活化，造成多巴胺神經活性衰退，大鼠上產生類似PD患者的睡眠障礙症狀，並藉由此模式來探討PD患者睡眠產生改變的機轉是否經過微膠細胞活化所釋放之細胞素 (cytoki...
For patients with the Parkinson’s disease (PD), the degeneration of dopaminergic neurons causes the decrease of dopamine release from the substantia nigra pars compecta (SNpc) to the striatum. It is also found that the PD patient’s brain has inclusion bodies of α-synuclein in this area. These inclusion bodies can lead to activate mitochondrial and to subsequently release cytokines, such as tumor necrosis factor – alpha (TNF-α) and interlukin-1beta (IL-1β), which affect the PD patient’s sleep. We herein used a proteasome inhibitor, MG-132, to inhibit the function of proteasome, which caused the loss of dopaminergic neurons in SNpc, and subsequently changed the sleep architecture in rats. The total amount of NREMS was significantly increased, and the of wakefulness was decreased during the dark-period at the 7th day after MG-132 treatment. We administered tumor necrosis factor receptor fragment (TNFRF) and interlukin-1 receptor antagonist (IL-1ra), to elucidate the involvement of TNF-α and IL-1β in MG-132-induced sleep alteration. The MG-132-induced sleep alteration was reversed after...
參考文獻:
1.1. Parkinson J. An essay on the shaking palsy. 1817. J Neuropsychiatry Clin Neurosci 2002;14(2):223-36.
連結：
2.3. Poewe W. Non-motor symptoms in Parkinson's disease. Eur J Neurol 2008;15 Suppl 1:14-20.
連結：
3.4. Ziemssen T, Reichmann H. Non-motor dysfunction in Parkinson's disease. Parkinsonism Relat Disord 2007;13(6):323-32.
連結：
4.6. Kageyama H, Takenoya F, Hori Y, Yoshida T, Shioda S. Morphological interaction between galanin-like peptide- and dopamine-containing neurons in the rat arcuate nucleus. Regul Pept 2008;145(1-3):165-8.
連結：
5.7. Frank MJ. Dynamic dopamine modulation in the basal ganglia: a neurocomputational account of cognitive deficits in medicated and nonmedicated Parkinsonism. J Cogn Neurosci 2005;17(1):51-72.
回應(0)