運動對於胚胎期暴露塑化劑母鼠之影響

The Effect of Exercise on Maternal Behaviors in the Gestational Phthalate-exposed Female Rats

李羿儒(Yi-Ju Lee)

指導教授 ： 王錠釧

高雄醫學大學/醫學院/運動醫學系碩士班/碩士(2018年)

摘要

科學界已經證實運動對於腦部功能的助益，以及早年不幸對於腦部功 能的害處。規律的運動能提升學習與記憶效果、降低神經退化性疾病的發 生，以及緩和焦慮與憂鬱的症狀。運動後所促進的腦泌神經滋養素 (brain-derived neurotrophic factor, BDNF) 在此過程扮演重要的角色，能夠增 進神經元的活性與受傷後的修復。此外，母性行為對於子嗣的生長與發育 能提供保障，主要是透過催產素的作用造成母性行為的表現與母嬰聯繫的 增強。母親若於幼年時遭遇不幸的經驗會使得催產素功能失調，通常會導 致 小 孩 行 為 改 變 ， 造 成 代 間 傳 遞 的 效 應 。 塑 化 劑 DEHP (di-(2-ethylhexyl)-phthalate) 為聚氯乙烯塑膠製品最常使用的成分，已被證實 為一種環境荷爾蒙，極易造成神經功能的傷害。雖然新生兒暴露於塑化劑 DEHP與成年後的壓力處理能力不良以及高度焦慮行為有密切相關，然而目 前尚無對於塑化劑DEHP影響母性行為的研究報告。由於運動誘導BDNF的 釋放能夠改善認知與情緒功能，因此本研究欲探討幼年期接觸塑化劑DEHP 的雌鼠，是否於成年後分娩哺乳時有情緒障礙與母性行為的偏差，以及進 行運動能否改善這種行為偏差，進而保障後代的身心健康。本研究以胚胎 期暴露DEHP的F1子代雌鼠進行為期9週的跑步機運動訓練，待其成年後懷 孕生產F2子代雌鼠。F1雌鼠觀察評估其焦慮行為與母性行為之後，以酵素 免疫分析法偵測血中BDNF、催產素、與皮質固酮的濃度。再以蛋白質電泳 分析下視丘的催產素接受器的表現量。研究結果發現胚胎期接觸塑化劑 DEHP會損害日後的母性行為，血漿催產素與下視丘催產素接受器表現量明 顯減少。進行運動訓練未能改善受損的母性行為。無論是否有運動，壓力 反應與血漿皮質固醇在各組織間均無顯著性差異。懷孕期暴露塑化劑DEHP， 對於子代雌鼠日後的母性行為會有破壞的效果，然而其壓力反應並不受塑化劑DEHP的影響。此外，胚胎期暴露塑化劑DEHP的母鼠在幼年期至青春 期進行有氧運動訓練無法恢復其日後產後之母性行為。

關鍵字

母性行為 ； 壓力 ； 反應運動 ； 塑化劑

並列摘要

Both the beneficial effects of exercise and the detrimental effects of early life adversity on brain function have been reported. Regular exercise can improve learning and memory, reduce risk of neurodegenerative diseases, and ameliorate symptoms of anxiety and depression. Exercise-induced release of the brain-derived neurotrophic factor (BDNF) plays a key role in this adaptation, which can promote neuronal survival and facilitate the recovery after injury. Meanwhile, maternal behavior has an important function in stimulating adequate growth and development of the offspring. The neuropeptide oxytocin coordinates the onset of maternal behavior and the enhancement of mother-infant bonding. Childhood adverse experiences received by a mother can lead to dysregulation of the oxytocin system, which usually induces phenotypic changes in the offspring, is commonly known as a transgenerational effect. Di-(2-ethylhexyl)-phthalate (DEHP), a plasticizer usually applied in polyvinyl chloride manufacture, is regarded as an endocrine disruptor to exert toxic effects on the nervous system. Although neonatal exposure to DEHP is associated with dysregulation of stress coping ability and higher rates of anxiety in adulthood, however, there is no study examining the effect of DEHP on maternal behavior. Because exercise-induced BDNF release improves cognitive and emotional functions, therefore, an attempt was made in the present study to evaluate the effects of exercise on ameliorating the interference neonatal DEHP exposure on maternal behavior. In this study, prenatal DEHP-exposed female rats of F1generation was trained to treadmill running for 9 weeks, and then were subjected to breed pups of F2 generation. The present study analyzed the DEHP-induced effects on anxiety-like behavior and maternal behavior of F1 generation of female rats. The blood levels of BDNF, oxytocin, and corticosterone were measured by enzyme-linked immunosorbent assay (ELISA).Proteins from hypothalamus wereanalyzed by Western blotting to examine the expressions of oxytocin receptor. The results showed that DEHP can impair the maternal behavior, and the plasma oxytocin levels and the expressions of oxytocin receptor are both reduced significantly. Meanwhile, treadmill running fails to restore the impaired maternal behavior, plasma oxytocin level, and the expression of oxytocin receptor. Interestingly, the stress response and plasma corticosterone levels show no significant difference among groups. In summary, prenatal exposure of DEHP may impair the maternal behaviors without affecting the stress response. Exercise during childhood to adult has little effect on ameliorating the impaired maternal behaviors in the prenatal DEHP-exposed female rats.

並列關鍵字

Maternal behavior ； Stress response ； Exercise ； Di-(2-ethylhexyl)-phthalate (DEHP)

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