利用初級細胞培養以及小鼠模式確認對阿茲海默氏症具治療潛力之中草藥

Identification of potential Chinese herbs for Alzheimer’s disease using primary culture and mouse models

黃景怡(Huang Chimg-Yi)

指導教授 ： 謝秀梅

國立臺灣師範大學/理學院/生命科學系/碩士(2016年)

https://doi.org/10.6345/NTNU202204367

摘要

阿茲海默氏症（Alzheimer’s disease; AD）是目前最常見的漸進式神經退化性疾病，主要因海馬迴的神經元受損而導致認知功能障礙。據估計，全球有超過3500萬人罹患AD。AD起始的主要關鍵為類澱粉胜肽(beta-amyloid peptides; Aβ)堆積和tau蛋白質的過度磷酸化。近期有愈來越多的證據顯示，對於多因性之疾病AD而言，使用多目標特性的傳統中草藥治療效果可能優於單靶藥物。因此，近年來中草藥於AD的研究和治療越來越受到重視。在此研究中，我們建立了以寡聚體Aβ25-35和Aβ42處理的初級海馬迴神經細胞平台進行中草藥的篩選，希望藉此篩選出具有神經保護功效的中草藥。從此篩藥平台中，我們發現NH037中草藥能有效的增加神經元數目、神經突起長度、神經突起分支數目，並伴隨提高無活性GSK3β的量及減少Aβ堆積與脂質氧化壓力等神經保護效果。更進一步，於兩側海馬迴CA1區域注射寡聚體Aβ25-35的C57BL/6 小鼠動物實驗中，我們也發現NH037中草藥可以減少小鼠的焦慮及認知功能異常的問題，而在病理分析中我們可以看到NH037前處理減少Aβ類澱粉蛋白質堆積、tau蛋白質磷酸化、神經發炎反應與增加突觸相關蛋白質表現量及正腎上腺素神經元與血清素神經元數目以對抗寡聚體Aβ25-35所造成的細胞毒性。因此， NH037可能有潛力避免認知、非認知損傷以及誘發AD相關的病因特性。

關鍵字

NH037 ； 神經保護 ； 寡聚體Aβ ； 認知 ； 焦慮

並列摘要

Alzheimer’s disease (AD) is the most common neurodegenerative disease associated with progressive damage in hippocampal neurons and cognitive dysfunctions. It is estimated that over 35 million people worldwide suffered from the disease. Both the accumulation of beta-amyloid peptides (Aβ) and tau protein phosphorylation are regarded as crucial events in the initiation of AD. Recently, more evidences show that the multi-target characteristics of traditional Chinese Herb Medicine (CHM) may be advantageous over single-target drugs against the multifactorial nature of AD. These drugs have therefore attracted much attention in the research and treatment in AD. In the present study, we established mouse primary hippocampal neuronal culture treated with oligomeric Aβ25-35 and Aβ42 as the screening platform of CHM. From the in vitro screening results , we found that CHM NH037 can prevent the decrease of neuronal number, neuritic length, branch number, lipid oxidation, amyloid deposition , and NH037 increasing the level of inactived GSK3β under neurotoxicity of oligomeric Aβ. Furthermore, the administration of NH037 also reduced anxiety and the cognitive impairment in the C57BL/6J mice treated with bilateral intrahippocampal CA1 injection of oligomeric Aβ25-35. From pathological analysis, we further found that the pretreatment of NH037 decreased the levels of Aβ deposition, tau protein phosphorylation, neuroinflammation, and increased the levels of synapse-related protein expression, noradrenergic and serotonergic neurons against the toxicity of oligomer Aβ25-35. Therefore, using CHM NH037 is a potential therapeutic strategy to prevent the cognitive, noncognitive dysfunction, and related pathogenic characterizations of AD.

並列關鍵字

NH037 ； neuroprotection ； oligomeric Aβ ； cognition ； anxiety

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