年輕大白鼠於哺乳期釩暴露所致小腦失能藉由有氧運動改善之效果評估

Ameliorating Effect of Aerobic Exercise on Motor Dysfunction in Lactational Vanadium-Exposed Young Rats

林鈺益(Yu-Yi Lin)

指導教授 ： 王錠釧

高雄醫學大學/醫學院/運動醫學系研究所/碩士(2014年)

https://doi.org/10.6832/KMU.2014.00141

摘要

重金屬釩 (vanadium) 為一種天然的過渡金屬元素，雖然釩常被用來製造合金、精密儀器及許多工業用途，但釩的化合物含有劇毒，會對中樞神經系統產生影響，並且影響動作反應及協調性。小腦於動作協調性扮演重要角色，在小腦發育階段暴露重金屬釩，已被證實會傷害小腦白質的發展。小腦的透過普金氏細胞 (purkinje cell) 的活化發揮其功能，普金氏細胞及其樹突上之樹突棘損傷會造成運動協調性失調。有氧運動可改善動作的不協調。已有許多文獻證實，有氧運動會增加血液及腦部腦源神經滋養因子 (brain-derived neurotrophic factor，BDNF) 的增加。然而，雖然重金屬釩暴露會對小腦白質產生影響，但對小腦神經元的損害仍不清楚，因此，透過哺乳過程在小腦發育關鍵期暴露重金屬釩，並藉由有氧運動訓練誘發BDNF功能，是否可以改善小腦受損情況，並增進其運動協調性。本實驗採用Sprague-Dawley新生雄性大白鼠，於出生後至三周齡藉由哺乳暴露重金屬釩，並於離乳後進行5周跑步機訓練。訓練結束後進行動作行為試驗，評估其動作協調性、自主運動能力以及步態。老鼠犧牲後採取其血液及小腦樣本，並以免疫酵素分析、電泳及免疫染色觀察小腦內結構及功能性。結果顯示重金屬釩暴露不會對自主運動能力及步態造成影響，但動作協調性有顯著降低，並且降低血液及小腦BDNF表現，增加普金氏細胞樹突棘密度。而透過運動訓練，可提升動作協調性，增加血液BDNF表現，並且使受釩暴露影響的樹突棘密度回復正常。哺乳期重金屬釩暴露，致使BDNF-TrkB路徑功能降低，影響小腦修飾樹突功能而造成其動作協調性受損。而透過有氧運動訓練，雖無法回復小腦BDNF表現，但藉由提升TrkB表現修復BDNF-TrkB路徑的缺損，使普金氏細胞完成發育期樹突棘修剪之程序，而可以改善釩暴露所帶來的協調性缺失。

關鍵字

釩 ； 有氧運動 ； 腦源神經滋養因子 ； 小腦 ； 樹突棘 ； 發育

並列摘要

Recent studies indicate that exercise have beneficial effects on the central nervous system, such as improving learning and memory, reducing the risk of neurodegenerative diseases, and providing protection against insults. Accumulated evidence show that release of brain-derived neurotrophic factor (BDNF) playing a key role in the adaptation of central nervous system to exercise. Early-life exercise can enhance capacity to evoke memories and reduced risk of neurodegenerative diseases in later life. This long-term effects of exercise-induced BDNF can maintain the structure and function of central nervous system, suggesting that exercise may be a useful method to ameliorate the adverse effects caused by insults in early life. In addition, because the brains of infant baby are more vulnerable to environmental toxic agents, early-life exposure to environmental toxic agents may result in increased risk of neural dysfunction in the adults. Furthermore, evidences suggest that vanadium, an important element in alloy manufacturing, is regarded as a candidate of environmental toxin and may cause health problems in humans. Postnatal exposure to sodium metavanadate (NaVO3) can impair the development of cerebellum by reducing the volume of cerebellar white matter in adult animals. Because exercise-induced BDNF release is assumed to protect against neurodegenerative diseases, therefore, an attempt is made in the present study to evaluate the effects of exercise on ameliorating the neonatal NaVO3 exposure-induced neural dysfunction in young adult rats. Sprague Dawley female rats were treated with NaVO3 (3 mg/kg per day, ip.) or vehicle during lactational period. After weaning (postnatal day 22), the male offspring were trained on treadmill running for 5 weeks. At the age of 2 months (late adolescent), animals were subjected to motor coordination test followed by biochemical examination of BDNF and histological examination of the cerebellum. The results showed that deficit of motor coordination, lower BDNF levels in plasma and cerebellum, and increased dendritic spine density were observed in NaVO3-exposed rats. These results indicated that NaVO3 exposure may interfere the pruning of dendritic spines on the cerebellar Purkinje cells by reducing the release of BDNF, leading to dysfunction of cerebellum. After the five-week aerobic exercise training program, the performances of motor coordination were improved in NaVO3-exposed rats. In addition, levels of BDNF and dendritic spine density were restored in the cerebellum of NaVO3-exposed rats after aerobic exercise. Given the findings of this study, it was proposed that aerobic exercise may provide beneficial effects on ameliorating the altered biochemical and neurobehavioral outcomes in lactational NaVO3-exposed young adult rats.

並列關鍵字

vanadium ； aerobic exercise ； brain-derived neurotrophic factor ； cerebellum ； dendritic spines ； development

參考文獻

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