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標題: | 靈芝與蟲草米複方萃取物於不可預期慢性溫和壓力動物模式中之抗憂鬱功效 The antidepressive effects of Ganoderma lucidum-Cordyceps militaris rice extract formula in unpredictable chronic mild stress animal model |
作者: | Wan-Ting Chang 張菀庭 |
指導教授: | 沈立言(Lee-Yan Sheen) |
關鍵字: | 憂鬱症,靈芝,蟲草米,記憶,神經可塑性, Depression,Ganoderma lucidum,Cordyceps militaris rice,memory,neuroplasticity, |
出版年 : | 2018 |
學位: | 碩士 |
摘要: | 世界衛生組織統計,全球逾 3 億人口患有憂鬱症,且預測在 2030 年將成為全球第一高負擔疾病,顯然憂鬱症為全球所須關注的議題。然而,藥物副作用造成病人服藥順應性不高,因此本研究希望找尋輔助治療,或以預防方式減少憂鬱症發生。研究指出,靈芝 (Ganoderma lucidum, GL) 中的三萜類可以增加神經滋養因子 (brain-derived neurotrophic factor, BDNF) 的濃度,有神經保護的效果。而蟲草米 (Cordyceps militaris rice, CMR) 為培養北蟲草之固態基質,富含北蟲草的活性成分蟲草素 (cordycepin),研究指出在不可預期慢性溫和壓力 (unpredictable chronic mild stress, UCMS) 模式中,蟲草素能提高小鼠的糖水偏好,因此蟲草米是有具抗憂鬱潛力之食材。本研究以此兩種材料組合成複方,希望能減少各材料之用量即達到抗憂鬱之功效,以降低因高劑量造成副作用之風險,同時節省成本增加產品開發時的競爭力。此外,有研究發現 UCMS 會使老鼠 BDNF 濃度下降,進而影響認知功能甚至是記憶,故本研究欲探討靈芝與蟲草米 (GL-CMR) 複方在 UCMS 模式中是否能改善類憂鬱行為及空間學習記憶能力,並分析大鼠腦部神經傳導物質與神經可塑性蛋白質表現。結果顯示本實驗之 UCMS 顯著降低大鼠的蔗糖水偏好,表示已誘導出類憂鬱行為,同時給予 GL-CMR 的組別顯著增加約 25% 蔗糖水攝取,且於莫氏水迷宮 (Morris water maze, MWM) 訓練期中,GL-CMR 的組別相較於負控制組 (negative control, NCTL) 有顯著較低的脫逃潛伏 (escape latency) 時間。此外,於海馬迴中,低劑量組相較 NCTL 顯著減少約 34% 血清素轉換率、中劑量組相較 NCTL 顯著減少約 50% 多巴胺轉換率;NCTL 較控制組有顯著較低的 phospho-protein kinase B (p-Akt)、phospho-cAMP response element-binding (p-CREB) 及 phospho-mammalian target of rapamycin (p-mTOR) 相對表現量,而給予 GL-CMR 的組別能顯著提升 p-CREB、p-Akt、p-mTOR 及 postsynaptic density protein 95 (PSD 95) 相對表現量,同時也使 BDNF 有增加趨勢,表示 GL-CMR 能回復因 UCMS 誘導所減少之神經可塑性的蛋白質表現。綜合上述結果證實 GL-CMR 能改善大鼠類憂鬱行為、促進 MWM 中學習記憶能力,且可能經由活化神經可塑性路徑達到抗憂鬱功效。 As shown in statistics by World Health Organization (WHO), there has been more than 300 million people suffering from depression. Depression has been the leading cause of disability worldwide for many years. WHO also predicts that depression will result in the highest global burden of disease by 2030. Obviously, depression is highly concerned nowadays. However, the side effects of antidepressants often make low compliance with medication in patients. Prevention of depression with complementary and alternative medicine is considered better than conventional therapies. A study showed that triterpenoids in Ganoderma lucidum (GL) could increase brain-derived neurotrophic factor (BDNF) to protect neurons. Cordyceps militaris rice (CMR), the solid-state medium for cultivation of Cordyceps militaris (CM), was found to rich with cordycepin, which can significantly increase sucrose preference of mice in an unpredictable chronic mild stress (UCMS) model. Thus, CMR is potential to exert antidepressant-like effects. In this study, I combined GL and CMR as a treatment and hypothesized it could use less dose of these two materials to exhibit the antidepressive effects. Besides, one study showed that UCMS decreased BDNF of rodents, and subsequently impacted on cognition and memory. Therefore, the purpose of this study is to investigate whether GL-CMR can reverse sucrose preference, and spatial learning memory. In addition, I analyzed neurotransmitters and neuroplasticity-related proteins in brains of UCMS-induced rats. Results showed that UCMS significantly decreased sucrose preference of rats, and GL-CMR could reverse it by 25%. In training trials of Morris water maze, GL-CMR could significantly decrease the escape latency compared to that of NCTL. In the hippocampus, turnover rate of serotonin in low dose group was lower than that of NCTL by 34%, and turnover rate of dopamine in medium dose group was lower than that of NCTL by 50%. Furthermore, expression of phospho-cAMP response element-binding protein (p-CREB), phospho-protein kinase B (p-Akt), phospho-mammalian target of rapamycin (p-mTOR) and postsynaptic density protein 95 (PSD 95) in NCTL decreased, by contrast, it could be reversed by treatment of GL-CMR. Also, expression of BDNF was increased by GL-CMR, indicating its capability of improving the neuroplasticity of rats. In conclusion, GL-CMR could reverse the depressive-like behaviors, improve learning memory, and have antidepressive effects by activating the pathways of neuroplasticity in UCMS-induced rats. |
URI: | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/79179 |
DOI: | 10.6342/NTU201802032 |
全文授權: | 有償授權 |
電子全文公開日期: | 2023-08-09 |
顯示於系所單位: | 食品科技研究所 |
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