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

Guo Zhu Sun, Yong Chang He, Xiao Kuang Ma, Shuang Tao Li, De Jie Chen, Ming Gao, Shenfeng Qiu, Jun Xiang Yin, Jiong Shi, Jie Wu

Research output: Contribution to journalArticle

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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.

Original languageEnglish (US)
Pages (from-to)748-758
Number of pages11
JournalCNS Neuroscience and Therapeutics
Volume23
Issue number9
DOIs
StatePublished - Sep 1 2017

Fingerprint

Apolipoprotein E4
Genes
Apolipoprotein E3
Dendritic Spines
Long-Term Potentiation
Memory Disorders
Carbachol
Apolipoproteins E
Synaptic Transmission
Synapses
Transgenic Mice
Hippocampus
Alzheimer Disease
Spine
Genotype
Learning

Keywords

  • apolipoprotein E4
  • dendrites
  • hippocampus
  • synaptic plasticity
  • theta oscillations

ASJC Scopus subject areas

  • Pharmacology
  • Psychiatry and Mental health
  • Physiology (medical)
  • Pharmacology (medical)

Cite this

Sun, G. Z., He, Y. C., Ma, X. K., Li, S. T., Chen, D. J., Gao, M., ... Wu, J. (2017). Hippocampal synaptic and neural network deficits in young mice carrying the human APOE4 gene. CNS Neuroscience and Therapeutics, 23(9), 748-758. https://doi.org/10.1111/cns.12720

Hippocampal synaptic and neural network deficits in young mice carrying the human APOE4 gene. / Sun, Guo Zhu; He, Yong Chang; Ma, Xiao Kuang; Li, Shuang Tao; Chen, De Jie; Gao, Ming; Qiu, Shenfeng; Yin, Jun Xiang; Shi, Jiong; Wu, Jie.

In: CNS Neuroscience and Therapeutics, Vol. 23, No. 9, 01.09.2017, p. 748-758.

Research output: Contribution to journalArticle

Sun, GZ, He, YC, Ma, XK, Li, ST, Chen, DJ, Gao, M, Qiu, S, Yin, JX, Shi, J & Wu, J 2017, 'Hippocampal synaptic and neural network deficits in young mice carrying the human APOE4 gene', CNS Neuroscience and Therapeutics, vol. 23, no. 9, pp. 748-758. https://doi.org/10.1111/cns.12720
Sun, Guo Zhu ; He, Yong Chang ; Ma, Xiao Kuang ; Li, Shuang Tao ; Chen, De Jie ; Gao, Ming ; Qiu, Shenfeng ; Yin, Jun Xiang ; Shi, Jiong ; Wu, Jie. / Hippocampal synaptic and neural network deficits in young mice carrying the human APOE4 gene. In: CNS Neuroscience and Therapeutics. 2017 ; Vol. 23, No. 9. pp. 748-758.
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