有氧運動訓練對早期亨丁頓氏舞蹈症小鼠運動生理功能的影響

Effects of Aerobic Exercise Training in Early Stage R6/2 Huntington's Disease Transgenic Mice

莊泰源(Tai-Yuan Chuang) ； 丁詩同(Shih-Torng Ding) ； 吳忠信(Chung-Hsin Wu)

《運動生理暨體能學報》 15輯 (2012/12) Pp. 27-38

https://doi.org/10.6127/JEPF.2012.15.04

摘要

亨丁頓氏舞蹈症（Huntington's disease, HD）為一種神經退化性疾病，是由於人類第四對染色體中的huntingtin（htt）基因產生突變，引起CAG三個核苷酸重複序列異常擴張，造成大量產生多麩醯胺片段（poly-glutamine tract, polyQ tract）蛋白質聚集，漸漸使得腦基底核附近的神經細胞退化或死亡，根據臨床的症狀指出，亨丁頓氏舞蹈症患者除了會出現認知與記憶功能退化外也會出現運動能力衰退的現象。前人的研究顯示，運動似乎對神經退化性疾病有所助益，然而運動是否會延緩亨丁頓氏舞蹈症的症狀，研究結果並非相當的一致。目的：本研究主要探討有氧運動訓練對初期亨丁頓氏舞蹈症小鼠生理功能的影響。方法：以亨丁頓氏舞蹈症R6/2基因轉殖小鼠及野生型（wild-type）小鼠為材料，隨機將其分成運動與不運動兩組，進行以下的實驗：一、以PhysioScan能量代謝系統測量小鼠的最大攝氧量，同時以動物跑步機測量小鼠衰竭時的最大跑步速度；二、以Rotarod測量小鼠之平衡與協調等綜合運動能力；三、以小動物血壓計測量小鼠血壓與心跳、四、進行後腿緊縮測驗（rear-paw clasping test）。所測得的實驗數據以混合設計二因子變異數分析法進行統計資料處理並以Tukey法進行處理組間比較。結果：不管是亨丁頓氏舞蹈症R6/2基因轉殖鼠或野生型小鼠，運動組比不運動組有以下影響：一、較高的最大攝氧量及最大跑步速度；二、較佳的平衡與協調能力；三、較低的平均血壓及安靜心跳率；四、較晚出現後腿緊縮的現象。結論：有氧運動訓練會提高亨丁頓氏舞蹈症早期小鼠的運動生理功能，這結果支持有氧運動訓練可能會延遲亨丁頓氏舞蹈症發病的時間及可能延長發病後的存活時間。

關鍵字

R6/2 HD基因轉殖小鼠 ； 最大攝氧量 ； 最大跑步速度 ； 後腿緊縮

並列摘要

Huntington's disease (HD) is a neurodegenerative disease that caused by abnormal CAG repeat expansions of huntingtin (htt) gene on chromosome 4. The htt gene encodes an extended poly-glutamine tract (poly-Q tract) in the Htt protein that leads to neurodegeneration in the brain. According to clinical symptoms of HD, the impaired exercise ability is often observable in patients with HD. Recent study has suggested that exercise benefits both general health and brain function in neurodegenerative diseases. However, it remains inconsistent whether exercise delays HD in particular. Purpose: The main objective of the our study was to investigate the effect of aerobic exercise training in early R6/2 Huntington's disease transgenic mice. Methods: Transgenic HD mice of the R6/2 line were originally purchased from the Jackson Laboratories (Bar Harbor, ME, USA). Following analyses were performed: (1) Measuring VO2max and maximum running speed by PhysioScan system and treadmill (AccuScan Instruments, Inc., USA); (2) measuring mice balance capability by Rota-rod; (3) determining blood pressure and heart beat rate by Sphygmomanometer (BP-2000 Blood Pressure Analysis System, Visitech system Inc., USA), and (4) testing rear-paw clasping reaction. All variables were statically analyzed by two-way ANOVA with Tukey post hoc test. Results: for both wild type and R6/2 mice, exercise group is superior to non-exercise control group in following comparisons. (1) better VO2max and running speed; (2) better balance and coordinate capability; (3) lower average blood pressure and less rest heart rate, and (4) late appear rear-paw claspinghind-limb clasping symptom. Conclusions: Aerobic exercise training enhances physiological function in early stage R6/2 transgenic mice which might delay disease onset and prolong host life span after disease onset.

並列關鍵字

R6/2HD transgenic mice ； VO2max ； maximum running speed ； rear-paw clasping

參考文獻

Altschuler, E. L.(2006).Strenuous, intensive, long-term exercise does not prevent or delay the onset of Huntington's disease.Medical Hypotheses.67(6),1429-1430.

Andrich, J.,Schmitz, T.,Saft, C.,Postert, T.,Kraus, P.,Epplen, J.(2002).Autonomic nervous system function in Huntington's disease.Journal of Neurology, Neurosurgery and Psychiatry.72(6),726-731.

Beal, M. F.(2000).Energetics in the pathogenesis of neurodegenerative diseases.Trends in Neurosciences.23(7),298-304.

Brinkman, R. R.,Mezei, M. M.,Theilmann, J.,Almqvist, E.,Hayden, M. R.(1997).The likelihood of being affected with Huntington disease by a particular age, for a specific CAG size.American Journal of Human Genetics.60(5),1202-1210.

Brown, J.,Cooper-Kuhn, C. M.,Kempermann, G.,Van Praag, H.,Winkler, J.,Gage, F.(2003).Enriched environment and physical activity stimulate hippocampal but not olfactory bulb neurogenesis.European Journal of Neuroscience.17(10),2042-2046.