小胶质细胞
转基因小鼠
发病机制
病理
表型
淀粉样蛋白(真菌学)
阿尔茨海默病
淀粉样变性
神经科学
生物
转基因
医学
炎症
免疫学
疾病
基因
生物化学
作者
Lisa Steinbrecher,Ann‐Christin Wendeln,Desirée Brösamle,Ping Liu,Katleen Wild,Lisa M. Haesler,Rawaa Al‐Shaana,Jonas J. Neher
摘要
Abstract Background Microglial cells play an important role in the pathogenesis of Alzheimer’s disease. We have previously shown that microglia activate the Hypoxia inducible factor‐1α (HIF‐1α) signalling pathway in response to cerebral β‐amyloidosis in a mouse model of Alzheimer’s pathology (Wendeln et al., Nature , 2018). Importantly, we also found that activation of microglial HIF‐1α signalling correlated with disease severity and that HIF‐1α levels were particularly elevated in plaque‐associated microglia. Method In the experiments presented here, we analyzed the role of microglial HIF‐1α in promoting cerebral β‐amyloidosis by characterizing pathological hallmarks and microglial activation states in two APP transgenic mouse models with an induced HIF‐1α knockout (KO) in microglia cells. Result Our results indicate that the lack of HIF‐1α in microglia increases their clustering around amyloid‐β plaques and alters the microglial phenotype and brain inflammatory state. While plaque load was indistinguishable in mice with/out microglial HIF‐1α, our data indicate that the increase in plaque‐associated microglia limits plaque‐induced neuronal damage. Conclusion Our data indicate that HIF‐1α inhibition alters the microglial phenotype, leading to an increased number of microglia around amyloid‐β plaques, thereby protecting neurons.
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