| Abstract: | 阿茲海默症 (Alzheimer’s disease, AD)為神經性退化疾病的一種，患者記憶力與認知功能下降，對家庭和社會造成極大負擔。阿茲海默症患者因海馬迴 (Hippocampus)出現磷酸化Tau蛋白和澱粉樣蛋白 (amyloid beta, Aβ)堆積，導致神經細胞大量死亡。研究顯示透過增加社交活動、運動或調整飲食來延緩疾病發展也是可以努力的方向。其中，地中海飲食 (Mediterranean diet)被證實可改善認知功能，膳食纖維發酵後產生的短鏈脂肪酸 (Short-chain fatty acid, SCFAs)可穿透血腦障壁 (blood-brain barrier, BBB)在腦部產生作用。研究指出AD患者腸道菌組成和SCFAs比例與健康人不同，我們選擇APP/PSEN1疾病鼠模式，利用物體辨別試驗(Novel Object Recognition Test, NORT)、水迷宮 (Morris water maze test, MWM)等不同行為學實驗評估小鼠記憶力與學習能力，也利用MRI腦部造影觀察腦區體積變化，並且透過腦、腸組織的組織切片和免疫染色實驗探討可能機轉，釐清SCFAs延緩AD病程的潛力。結果顯示短鏈脂肪酸不會影響老鼠活動能力，但可改善小鼠認知功能，延緩小鼠海馬迴萎縮程度，我們也觀察到短鏈脂肪酸改變腸道菌組成比例。本研究成果可做為未來應用於AD臨床輔助治療的參考。
Alzheimer’s disease (AD) is a neurodegenerative disorder that causes memory loss and cognitive impairment. The pathology of Alzheimer’s disease is characterized by the accumulation of amyloid beta (Aβ) plaques and tau protein in the hippocampus. Therapies that target Aβ have been the focus of efforts to develop a disease modification treatment for AD, beyond Aβ hypothesis, there are many strategies to help AD patients such as increasing exercise and social activities, and diet habits to affect the progress of disease. Mediterranean diet has been proven that it may slow down the development of AD, and Short-chain fatty acids (SCFAs) will pass through the blood-brain barrier after the fermentation of dietary fiber. Thus, AD patients’ gut microbiota composition and SCFA proportion are different from healthy people. Therefore, our study aims to clarify the role of SCFAs in AD progression. To prove this hypothesis, we use APP/PSEN1 mice model to evaluate the effect of different doses of SCFAs and conduct Novel Object Recognition Test and Morris water maze test to access mice’s cognitive and spatial memory, and magnetic resonance imaging for the volume change in the hippocampus, analysis the epithelium of intestinal tissue further investigates the signal transduction pathway. We found that SCFAs increased mice’s recognition index in NORT and improved spatial memory without affecting their locomotor activity in MWM. Moreover, SCFAs slow down the atrophy of hippocampal regions and microbiome composition changes after treatment. Our findings provide the potential strategy for the clinical adjuvant therapy of AD in the future. |
