神经毒性
体内
神经退行性变
β淀粉样蛋白
药理学
促炎细胞因子
淀粉样蛋白(真菌学)
海马体
阿尔茨海默病
体外
医学
化学
神经科学
生物
生物化学
毒性
病理
免疫学
内科学
疾病
炎症
生物技术
作者
Julie Colin,Ahmad Allouche,Sophie Hidalgo,Estelle Lager,Sandrine Lemoine,Christophe Müller,Pascale Rozan,Jean‐François Bisson,Nicolas Violle
出处
期刊:PubMed
日期:2021-12-01
卷期号:17 Suppl 3: e054152-e054152
摘要
The etiology of Alzheimer's disease (AD) is poorly understood. A growing body of literature suggests that amyloid beta oligomers (AβO) as the root cause of this disease. Here, we describe new translational in vitro and in vivo models of AD, induced by minute amount of in-house preparation of human AβO.AβO were reproducibly prepared from human Aβ 1-42 monomers. Rodent primary neurons were used to assess the neurotoxic activities of AβO in vitro and elderly wild-type mice administered by a single intracerebral injection AβO in vivo.The oligomeric preparations were characterized by SDS-page, electron microscopy and dot-plot tests. In vitro, AβO induced a dose-dependent neurodegeneration on rodent primary neurons based on various read-outs. Interestingly, neurotoxicity was greater with AβO than fibrillar Aβ, while Aβ monomers did not induce any neuronal damage. AβO-induced neurotoxicity was significantly attenuated by brain-derived neurotrophic factor (BDNF). In vivo, a single intracerebral microinjection of AβO in 18-month-old wild-type mice, led to a significant memory impairment, synaptic loss in hippocampus and increased secretion of brain proinflammatory cytokines 15 days post administration. Moreover, the memory deficits were significantly reversed with Donepezil used as reference drug.In conclusion, we characterized new tools for drug screening based on the soluble AβO hypothesis of AD. In vivo, this new non-inherited Alzheimer model can be used both to evaluate disease modifying and symptomatic drugs. Finally, these models are also valuable tools to understand the mechanisms underlying AD.
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