Sun Guo-Zhu, He Yong-Chang, Ma Xiao Kuang, Li Shuang-Tao, Chen De-Jie, Gao Ming, Qiu Shen-Feng, Yin Jun-Xiang, Shi Jiong, Wu Jie
Department of Neurosurgery, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei, China.
Department of Neurobiology, Barrow Neurological Institute, St. Joseph's Hospital and Medical Center, Phoenix, AZ, USA.
CNS Neurosci Ther. 2017 Sep;23(9):748-758. doi: 10.1111/cns.12720. Epub 2017 Aug 7.
Apolipoprotein E4 (APOE4) is a major genetic risk factor for late-onset sporadic Alzheimer disease. Emerging evidence demonstrates a hippocampus-associated learning and memory deficit in aged APOE4 human carriers and also in aged mice carrying human APOE4 gene. This suggests that either exogenous APOE4 or endogenous APOE4 alters the cognitive profile and hippocampal structure and function. However, little is known regarding how Apoe4 modulates hippocampal dendritic morphology, synaptic function, and neural network activity in young mice.
In this study, we compared hippocampal dendritic and spine morphology and synaptic function of young (4 months) mice with transgenic expression of the human APOE4 and APOE3 genes.
Hippocampal dendritic and spine morphology and synaptic function were assessed by neuronal imaging and electrophysiological approaches.
Morphology results showed that shortened dendritic length and reduced spine density occurred at hippocampal CA1 neurons in Apoe4 mice compared to Apoe3 mice. Electrophysiological results demonstrated that in the hippocampal CA3-CA1 synapses of young Apoe4 mice, basic synaptic transmission, and paired-pulse facilitation were enhanced but long-term potentiation and carbachol-induced hippocampal theta oscillations were impaired compared to young Apoe3 mice. However, both Apoe genotypes responded similarly to persistent stimulations (4, 10, and 40 Hz for 4 seconds).
Our results suggest significant alterations in hippocampal dendritic structure and synaptic function in Apoe4 mice, even at an early age.
载脂蛋白E4（APOE4）是晚发性散发性阿尔茨海默病的主要遗传风险因素。新出现的证据表明，老年APOE4人类携带者以及携带人类APOE4基因的老年小鼠存在与海马相关的学习和记忆缺陷。这表明外源性APOE4或内源性APOE4都会改变认知特征以及海马结构和功能。然而，关于Apoe4如何调节幼鼠海马树突形态、突触功能和神经网络活动，我们知之甚少。
在本研究中，我们比较了转人类APOE4和APOE3基因的年轻（4个月）小鼠的海马树突和棘突形态以及突触功能。
通过神经元成像和电生理方法评估海马树突和棘突形态以及突触功能。
形态学结果显示，与Apoe3小鼠相比，Apoe4小鼠海马CA1神经元的树突长度缩短，棘突密度降低。电生理结果表明，与年轻的Apoe3小鼠相比，年轻的Apoe4小鼠海马CA3-CA1突触的基本突触传递和双脉冲易化增强，但长时程增强和卡巴胆碱诱导的海马θ振荡受损。然而，两种Apoe基因型对持续刺激（4、10和40Hz，持续4秒）的反应相似。
我们的结果表明，即使在幼年时，Apoe4小鼠的海马树突结构和突触功能也有显著改变。
