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  • 學位論文

探討天麻水萃物在慢性社交挫敗壓力模式中之行為改善效果與腦部神經可塑性調節作用

Improvement of Stress-induced Behavior by Water Extract of Gastrodia elata Bl. on Brain Neuroplasticity Regulation in Chronic Social Defeat Stress Model

指導教授 : 沈立言
本文將於2027/02/13開放下載。若您希望在開放下載時收到通知,可將文章加入收藏

摘要


憂鬱症是嚴重的精神疾病之一,全球約有超過三億五千萬人口患有憂鬱症。然而現行憂鬱症藥物治療仍有許多不良反應。因此尋求具有抗憂鬱功效之保健食品或替代療法來預防及輔助治療憂鬱症有其必要性。天麻 (Gastrodia elata Blume) 過去常被用於傳統中醫及食療,可用來改善眩暈、癲癇及癱瘓。先前本實驗室以蛋白質體學方法探討天麻水萃物 (water extract of Gastrodia elata Blume, WGE) 之抗憂鬱機轉,發現其可能透過刺激神經可塑性而達到抗憂鬱效果。本研究之目的旨在更進一步探討天麻水萃物在小鼠慢性社交挫敗壓力模式下,其抗憂鬱功效及對神經可塑性調節之機制。實驗期以管餵給予C57BL/6小鼠WGE持續24天,於管餵第14天起同時給予慢性社交挫敗壓力,並以社交互動試驗、蔗糖偏好試驗及開放空間試驗來評估小鼠憂鬱行為。結果顯示餵食WGE (500 mg/kg BW) 有效改善慢性社交挫敗壓力所引起之體重停滯、過度攝食症狀及多渴症狀,並且在社交互動試驗改善壓力引起之社交迴避行為。除此之外,WGE可以調節因壓力而升高之皮質固醇濃度,並且增加海馬迴腦源性神經滋養因子 (Brain-derived neurotrophic factor) 之表現,此外亦提升海馬迴環化單磷酸腺苷反應元件結合蛋白 (cAMP response element binding protein, CREB) 與蛋白質激酶B (Protein kinase B, AKT) 磷酸化型態之表現。綜合以上結果,WGE可以減緩在慢性社交挫敗壓力模式中小鼠之類憂鬱行為並增加海馬迴中腦源性神經滋養因子相關路徑表現,可見WGE未來在協助憂鬱症預防及治療上具有相當潛力。

並列摘要


Depression is a common mental disorder. World Health Organization estimated 350 million people suffering from depression. However, the current antidepressant therapy was ineffective and unsatisified due to side effects. Many studies have reported that using functional foods are potential to be an adjunctive strategy to improve clinical symptoms of depression. Gastrodia elata Blume, a traditional Chinese medicine has been commonly used to treat dizziness, convulsion, and epilepsy since ancient times. Previous studies showed that water extract of Gastrodia elata Blume (WGE) possess antidepressive effect by modulating neuroplasticity -related pathway in proteomics. The aim of this study was using chronic social defeat stress model to investigate the antidepressant effect of water extract of Gastrodia elata Blume and its mechanism of neuroplasticity regulation. C57BL/6 mice were supplemented with WGE for 14 days by oral administration, and then conducted social defeat stress for 10 days with WGE. Mice were evaluated the depressive behaviors by social interaction test, sucrose preference test and open field test. The results showed that oral administration WGE (500 mg/kg BW) improved weight stagnation, hyperphagia symptoms and polydipsia symptoms. Moreover, WGE attenuated stress-induced social avoidance behavior and corticosteroid hyperactivity. In addition, WGE not only increased brain-derived neurotrophic factor (BDNF) expression, but also promoted phosphorylation of cAMP response element binding protein (CREB) and Protein kinase B (AKT) in hippocampus. Collectively, these findings demonstrated that WGE attenuated depress-like behavior and increases hippocampus BDNF-related signaling pathway in social defeat stress-induced mice. Thus, WGE could be a potential therapeutic agent for antidepression treatment in humans in the near future.

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