淀粉样蛋白-β诱导的内嗅皮层-海马网络神经元功能障碍的突触间进展。
Transsynaptic progression of amyloid-β-induced neuronal dysfunction within the entorhinal-hippocampal network.
机构信息
Gladstone Institute of Neurological Disease, San Francisco, CA 94158, USA.
出版信息
Neuron. 2010 Nov 4;68(3):428-41. doi: 10.1016/j.neuron.2010.10.020.
Abstract
The entorhinal cortex (EC) is one of the earliest affected, most vulnerable brain regions in Alzheimer's disease (AD), which is associated with amyloid-β (Aβ) accumulation in many brain areas. Selective overexpression of mutant amyloid precursor protein (APP) predominantly in layer II/III neurons of the EC caused cognitive and behavioral abnormalities characteristic of mouse models with widespread neuronal APP overexpression, including hyperactivity, disinhibition, and spatial learning and memory deficits. APP/Aβ overexpression in the EC elicited abnormalities in synaptic functions and activity-related molecules in the dentate gyrus and CA1 and epileptiform activity in parietal cortex. Soluble Aβ was observed in the dentate gyrus, and Aβ deposits in the hippocampus were localized to perforant pathway terminal fields. Thus, APP/Aβ expression in EC neurons causes transsynaptic deficits that could initiate the cortical-hippocampal network dysfunction in mouse models and human patients with AD.
摘要
内嗅皮层（entorhinal cortex，EC）是阿尔茨海默病（Alzheimer's disease，AD）最早受影响且最脆弱的大脑区域之一，与许多大脑区域的淀粉样蛋白-β（amyloid-β，Aβ）积累有关。突变型淀粉样前体蛋白（amyloid precursor protein，APP）选择性地在 EC 的 II/III 层神经元中过度表达，导致具有广泛神经元 APP 过度表达的小鼠模型出现认知和行为异常，包括多动、去抑制和空间学习记忆缺陷。EC 中的 APP/Aβ 过度表达会引起齿状回和 CA1 中突触功能和与活动相关分子的异常，以及顶叶皮层的癫痫样活动。在齿状回中观察到可溶性 Aβ，而海马中的 Aβ 沉积定位于穿通通路末端场。因此，EC 神经元中的 APP/Aβ 表达会导致突触传递缺陷，从而引发 AD 小鼠模型和人类患者的皮质-海马网络功能障碍。
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