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研究生:鐘悅慈
研究生(外文):Jhong, Yue-Cih
論文名稱:跑步運動訓練後給予低溫暴露減弱運動所誘發之對抗MPTP毒性的神經保護效果
論文名稱(外文):Cold exposure after exercise attenuates exercise-induced neuroprotection against MPTP toxicity
指導教授:莊季瑛莊季瑛引用關係
指導教授(外文):Chuang, Jih-Ing
口試委員:楊尚訓陳珮君
口試委員(外文):Shang-Hsun YangPei-Chun Chen
口試日期:2017-07-24
學位類別:碩士
校院名稱:國立成功大學
系所名稱:生理學研究所
學門:醫藥衛生學門
學類:醫學學類
論文種類:學術論文
論文出版年:2017
畢業學年度:105
語文別:英文
論文頁數:33
中文關鍵詞:運動低溫暴露MPTP
外文關鍵詞:exercisecold exposureMPTP
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運動訓練已知有許多的好處:包括增進心血管以及大腦功能等。在我們實驗室先前的研究已經顯示,運動訓練可以保護多巴胺神經細胞免於 N-甲基-4-苯基啶離子 (MPP+) 的毒殺。在運動過程中不能避免地會產生大量的熱能,而許多研究也已經證實:給予肌肉冰敷可以有效降低運動過程中產生的急性發炎。此外,在體溫較低 (32-35°C) 的情況下,有研究也顯示出具有保護神經的效果。然而低溫對於運動所誘發的神經保護作用仍是未知,因此我們想了解透過降低體溫來減弱運動過程中所產生的熱能,是否會對運動所造成的保護神經效果有影響。N-甲基-4-苯基-1,2,3,6-四氫吡啶 (MPTP) 會誘發氧化壓力並使黑質區投射到紋狀體的多巴胺神經細胞大量死亡,因此常被用來作為誘發帕金森氏症實驗模式的藥物。我們在連續的五天內,將 MPTP 經由腹腔注射到實驗小鼠 (C57BL/6) 體內,劑量為每天/ 每公斤體重 25 毫克,在第五針 MPTP 注射後的第二天讓實驗動物進行為期四週/ 每週五天/ 每天一小時的跑步運動訓練,並且在每天跑步運動結束後將實驗動物暴露在室溫 (22°C) 或者是冷房 (4°C) 中達兩小時。首先,我們觀察到 MPTP 會暫時性的降低實驗動物的腹腔溫度以及腦溫,卻不會影響節律體溫。我們也看到腹腔溫度和腦溫在運動過程中升高,然而只有腦溫在兩小時的 4°C 暴露中下降。再者,於運動後給予 4°C 暴露的條件下,節律體溫會些微的升高,且會促使運動過程中腹腔溫度及腦溫的增加更明顯。然而,上述所描述的運動或者 4°C 暴露的情況下,所造成的腹腔溫度變化並不會受到 MPTP 的影響。在實驗動物行為上我們也觀察到:小鼠在滾輪測試儀 (Rotarod) 上所能夠維持的時間會受到 MPTP 的影響而下降;跑步機運動訓練則會增加維持的時間並且改善 MPTP 所造成的影響。在免疫組織結果染色中,我們發現運動或是 4°C 暴露,可以避免由 MPTP 所造成的多巴胺神經細胞死亡及其所導致的行為缺失;這樣的現象在運動後給予 4°C 暴露時則會消失。 綜合上述,我們的研究指出運動過程中所短暫造成的輕微體溫上升以及運動後較低的節律體溫對於神經細胞是有保護效果的;然而,運動後給予 4°C 暴露則會干擾運動所誘發的體溫調節反應進而造成神經保護效果減弱。
Exercise is known to improve cardiovascular and brain function. Our previous results show that treadmill exercise training prevents the MPP+ (1-methyl-4-phenylpyridinium)-induced nigrostriatal neurodegeneration. It is also known that exercise-induced heat is inevitable and cryotherapy on muscle after exercise is a standard care for prevention from acute inflammation. Moreover, mild hypothermia (32-35°C) has been documented to exert neuroprotection. However, it remains unknown for the role of hypothermia in the exercise-induced neuroprotection. Herein, we attempted to investigate whether the 4°C cold exposure after exercise affect exercise-induced neuroprotection using the MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, a precursor of MPP+)-induced parkinsonian mouse model. Two days after intraperitoneal injection with MPTP (25 mg/kg/day, for five consecutive days), male C57BL/6 mice were subjected to treadmill exercise for 4 weeks (1 h/day, 5 days/week). After daily exercise training, mice were immediately exposed to 22°C room or 4°C cold temperature chamber for two hours. We found that MPTP induced a transient decrease in both body and brain temperature without changing circadian rhythm of body temperature which represents the oscillation within a day. Both body and brain temperatures were increased during one hour of treadmill running and decreased in the following two hours after running. The sedentary mice with cold exposure after exercise induced a sustained increase in circadian body temperature in contrast to daily cold exposure mice. Moreover, mice showed exercise-induced hyperthermia after daily post-exercise cold exposure. However, the exercise or cold exposure induced thermal responses were not affected by MPTP treatment. Treadmill ameliorated MPTP-induced motor impairment evaluated by the rotarod. Exercise training or daily cold exposure prevented dopaminergic neurodegeneration from MPTP insult, while cold exposure after exercise blocked the exercise-induced neuroprotection and motor improvement. The results suggested that exercise-induced mild hyperthermia and the following lower circadian body temperature is protective; however, the cold exposure after exercise disrupted the exercise-induced thermal response and impeded the neuroprotection.
中文摘要-I
Abstract-III
謝誌-V
Contents-VI
Introduction-1
Parkinson’s disease-1
Pathological feature of Parkinson’s disease-1
Animal models of Parkinson’s disease-1
Brain and body temperature on PD patients and parkinsonian animal models-2
Brain temperature-3
Generation of brain temperature-3
Characteristic of brain temperature-3
Brain temperature fluctuations under physical activity conditions-4
Beneficial effects of physical exercise in Parkinson’s disease-5
Effects of cryotherapy on exercise-triggered inflammation on muscle-6
Research rationales and hypothesis-8
Specific aims-8
Materials and methods-9
Animals-9
MPTP treatment-9
Measurement of striatal temperature in brain-9
Measurement of intraperitoneal body temperature-10
Exercise training and post-exercise cold exposure protocol-10
Rotarod test-11
Histological examination and immunocytochemistry of brain-12
Cell counting and image quantification-12
Statistical analysis-13
Results-14
The effects of treadmill running, MPTP injection, and 4°C exposure on circadian body temperature rhythm-14
The effect of MPTP on body temperature and brain temperature-15
The effect of treadmill running and 4°C exposure on body temperature-15
The effect of treadmill running and 4°C exposure on brain temperature-16
The effects of exercise and post-exercise 4°C exposure on MPTP-induced motor impairment-17
The effects of exercise and post-exercise 4°C exposure on MPTP-induced nigrostriatal DA neurodegeneration-18
Discussion-19
References-21
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