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Hippocampal synaptic and neural network deficits in young mice carrying the human APOE4 gene.


ABSTRACT:

Introduction

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.

Aim

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.

Methods

Hippocampal dendritic and spine morphology and synaptic function were assessed by neuronal imaging and electrophysiological approaches.

Results

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).

Conclusion

Our results suggest significant alterations in hippocampal dendritic structure and synaptic function in Apoe4 mice, even at an early age.

SUBMITTER: Sun GZ 

PROVIDER: S-EPMC6492660 | biostudies-literature | 2017 Sep

REPOSITORIES: biostudies-literature

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Hippocampal synaptic and neural network deficits in young mice carrying the human APOE4 gene.

Sun Guo-Zhu GZ   He Yong-Chang YC   Ma Xiao Kuang XK   Li Shuang-Tao ST   Chen De-Jie DJ   Gao Ming M   Qiu Shen-Feng SF   Yin Jun-Xiang JX   Shi Jiong J   Wu Jie J  

CNS neuroscience & therapeutics 20170807 9


<h4>Introduction</h4>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 morpholog  ...[more]

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