早期海马尖波涟漪缺陷可预测阿尔茨海默病小鼠模型的后期学习和记忆损伤。
Early Hippocampal Sharp-Wave Ripple Deficits Predict Later Learning and Memory Impairments in an Alzheimer's Disease Mouse Model.
机构信息
Gladstone Institute of Neurological Disease, San Francisco, CA 94158, USA; Biomedical Sciences Graduate Program, University of California, San Francisco, San Francisco, CA 94143, USA.
Kavli Institute for Fundamental Neuroscience and Department of Physiology, University of California, San Francisco, San Francisco, CA 94143, USA; Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA.
出版信息
Cell Rep. 2019 Nov 19;29(8):2123-2133.e4. doi: 10.1016/j.celrep.2019.10.056.
Alzheimer's disease (AD) is characterized by progressive memory loss, and there is a pressing need to identify early pathophysiological alterations that predict subsequent memory impairment. Hippocampal sharp-wave ripples (SWRs)-electrophysiological signatures of memory reactivation in the hippocampus-are a compelling candidate for this purpose. Mouse models of AD show reductions in both SWR abundance and associated slow gamma (SG) power during aging, but these alterations have yet to be directly linked to memory impairments. In aged apolipoprotein E4 knockin (apoE4-KI) mice-a model of the major genetic risk factor for AD-we find that reduced SWR abundance and associated CA3 SG power predicted spatial memory impairments measured 1-2 months later. Importantly, SWR-associated CA3 SG power reduction in young apoE4-KI mice also predicted spatial memory deficits measured 10 months later. These results establish features of SWRs as potential functional biomarkers of memory impairment in AD.
阿尔茨海默病（AD）的特征是进行性记忆丧失，因此迫切需要确定能够预测随后记忆损伤的早期病理生理改变。海马体中的尖波涟漪（SWR）——海马体中记忆再激活的电生理特征——是实现这一目标的有力候选者。AD 的小鼠模型在衰老过程中表现出 SWR 丰度和相关慢波（SG）功率的降低，但这些改变尚未与记忆损伤直接相关。在载脂蛋白 E4 基因敲入（apoE4-KI）小鼠——AD 的主要遗传风险因素的模型中——我们发现 SWR 丰度降低和相关 CA3 SG 功率降低可预测 1-2 个月后测量的空间记忆损伤。重要的是，年轻 apoE4-KI 小鼠的 SWR 相关 CA3 SG 功率降低也预测了 10 个月后测量的空间记忆缺陷。这些结果确立了 SWR 的特征作为 AD 中记忆损伤的潜在功能生物标志物。
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