探討魚油補充對去卵巢大鼠空間學習記憶及焦慮憂鬱之影響

Effects of fish oil supplementation on spatial learning, anxiety and depression in ovariectomized rats

林建融(Jian-Rong Lin)

指導教授 ： 蘇慧敏

國立臺灣大學/醫學院/生理學研究所/碩士(2010年)

https://doi.org/10.6342/NTU.2010.03101

摘要

婦女停經後，體內雌激素 (estrogen) 含量下降，對某些婦女而言，容易造成認知功能及情緒上的障礙。雌激素補充療法雖能有效改善停經婦女的認知功能以及焦慮、憂鬱等情緒，然而卻也增加罹患乳癌的風險。因此發展其他方式改善停經婦女的認知功能下降及情緒障礙，便是一個重要的課題。
根據研究顯示，雌激素與二十二碳六烯酸 (DHA，docosahexaenoic acid) ，均能幫助學習記憶 (learning and memory) 並改善焦慮 (anxiety) 及憂鬱(depression) 等情緒。而雌激素與DHA 在體內含量似乎有某種程度的關聯。因此本論文探討，是否能藉由補充富含DHA 的魚油，進而改善去卵巢大鼠因雌激素缺造成的學習記憶功能下降，並降低大鼠焦慮憂鬱的程度。
本研究將出生後六個月的Wistar 大鼠分成四組： 假手術組(sham operation)、去卵巢組 (ovariectomy)、假手術魚油補組、去卵巢魚油補充組。手術4 個月後開始進行行為實驗，測試大鼠空間參考記憶(spatial reference memory) 、工作記憶 (working memory) 以及焦慮、憂鬱的程度，並於鼠齡為12個月時將大鼠犧牲，分別對與學習記憶功能相關的海馬 (hippocampus) 與基底前腦 (basal forebrain) 進行組織切片染色；觀察海馬齒狀回(dentate gyrus) 神經新生 (neurogenesis)，計算齒狀回體積及CA1 (cornu ammonis 1) 神經細胞面積，並計算基底前腦內膽鹼神經元 (cholinergic neuron) 的細胞數。另一方面對情緒相關的背側縫核 (dorsal raphe) 進行組織切片染色，計算其內血清素神經元(serotonergic neuron) 的細胞數。
實驗結果發現去卵巢大鼠相較於假手術大鼠，在工作記憶實驗的表現較差；給予魚油補充的大鼠相較於未補充魚油的大鼠，在空間參考記憶及工作記憶實驗的表現均較佳，且魚油補充能提高大鼠齒狀回的神經新生能力，且能減少齒狀回IV因去除卵巢後造成的體積下降。然而去除卵巢或補充魚油並未對大鼠CA1 神經細胞面積、基底前腦膽鹼神經元細胞數造成顯著的影響。而在焦慮、憂鬱程度及血清素神經元細胞數方面，去除卵巢或魚油補充也無顯著影響。
根據本論文的實驗結果，推測魚油補充可能藉由增加齒狀回神經新生的能力，避免齒狀回因去除卵巢而減少體積，進而增進大鼠的空間參考記憶及工作記憶，因此或許能利用魚油的補充，幫助缺乏雌激素之停經婦女的學習記憶能力。

關鍵字

魚油 ； 去卵巢大鼠 ； 空間學習記憶 ； 焦慮 ； 憂鬱 ； 海馬 ； 神經新生

並列摘要

Cognitive decline and mood disorder may happen in postmenopausal women. Estrogen replacement therapy can delay cognitive decline, reduce the risk of Alzheimer’s disease and prevent mood disorder. However the therapy increases the risk of breast cancer in postmenopausal women. Therefore, it is important to find an alternative way to ameliorate the cognition and mood in postmenopausal women.
Docosahexaenoic acid (DHA, 22:6n-3) and estrogen have similar effects on neurological function. According to some studies, the concentration of DHA is related to that of estrogen in human body. The aim of this thesis is to study whether DHA enriched fish oil supplementation would prevent the decline of learning and memory and ameliorate anxiety and depression in ovariectomized rats. Six-month- old female rats were ovariectomized or sham operated and then fed n-3 fatty acids deficient diet with or without fish oil supplementation for six months. We hypothesized that ovariectomy (OVX) may decrease the ability of learning and memory, dentate gyrus volume, CA1 neuron cell size, neurogenesis in hippocampus, the number of cholinergic neurons in basal forebrain. Moreover, OVX may decrease the number of serotonergic neurons in dorsal raphe leading to anxiety and depression. While, fish oil
supplementation may retrieve back those changes.
We found that ovariectomized rats showed significantly poorer working memory than sham operated rats and fish oil supplementation rescued the memory performance. In addition, fish oil supplementation increase hippocampal neurogenesis in ovariectomized rats. Decreasing size of dentate gyrus in ovariectomized rats was ameliorated by fish oil supplementation. In CA1 neuron size and the number of cholinergic neurons, there was no significant difference between ovariectomized and sham operated rats with or without fish oil supplementation. On the other hand, there was no significant effect of OVX or fish oil supplementation on anxiety, depression and the number of serotonergic neurons.
According to our study, fish oil supplementation improves working memory and increases hippocampal neurogenesis in ovariectomized rats. These results suggest that fish oil supplementation has the benefit on learning and memory in postmenopausalwomen.

並列關鍵字

fish oil ； ovariectomized rats ； spatial learning ； anxiety ； depression ； hippocampus ； neurogenesis

參考文獻

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