Hippocampal synaptic and neural network deficits in young mice carrying the humanAPOE 4 gene
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Summary: Introduction: Apolipoprotein E4 (APOE 4) is a major genetic risk factor for late‐onset sporadic Alzheimer disease. Emerging evidence demonstrates a hippocampus‐associated learning and memory deficit in agedAPOE 4 human carriers and also in aged mice carrying humanAPOE 4 gene. This suggests that either exogenous APOE 4 or endogenous APOE 4 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 humanAPOE 4 andAPOE 3 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 CA 1 neurons in Apoe4 mice compared to Apoe3 mice. Electrophysiological results demonstrated that in the hippocampal CA 3‐CA 1 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.
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Previous studies have reported LTP deficits in APOE4-carrying mice compared to APOE3-carrying mice, in addition to morphological alterations in CA1 hippocampal neurons such as shortened dendritic length, reduced spine density, decreased levels of the presynaptic glutamatergic transporter vGLUT and GABAergic interneuron loss.
“Previous studies have reported LTP deficits in APOE4-carrying mice compared to APOE3-carrying mice, in addition to morphological alterations in CA1 hippocampal neurons such as shortened dendritic length, reduced spine density, decreased levels of the presynaptic glutamatergic transporter vGLUT and GABAergic interneuron loss [79–81].”
From Analysis of early effects of human APOE isoforms on Alzheimer’s disease and type III hyperlipoproteinemia pathways using knock-in rat models with humanized APP and APOE (2024) · cites this paper as [79]
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“…in APOE4 -carrying mice compared to APOE3 -carrying mice, in addition to morphological alterations in CA1 hippocampal neurons such as shortened dendritic length, reduced spine density, decreased levels of the presynaptic glutamatergic transporter vGLUT and GABAergic interneuron loss [79–81].”
Background
- Authors
- Sun, G., He, Y., Ma, X. K., Li, S., Chen, D., Gao, M., Qiu, S., Yin, J., Shi, J., & Wu, J.
- Affiliations
- Department of Neurosurgery The Second Hospital of Hebei Medical University Shijiazhuang Hebei China
- Barrow Neurological Institute (US)
- Department of Neurobiology Barrow Neurological Institute St. Joseph's Hospital and Medical Center Phoenix AZ USA
- Department of Basic Medical Sciences University of Arizona College of Medicine Phoenix AZ USA
- Department of Neurology Barrow Neurological Institute St. Joseph's Hospital and Medical Center Phoenix AZ USA
- Corresponding author
- Wu, Jie
- Venue
- CNS Neuroscience & Therapeutics
- Publisher
- Wiley
- Published
- 2017-08-07
- Volume
- 23
- Issue
- 9
- Pages
- 748-758
- ISSN
- 1755-5930 (ISSN-L)
- 1755-5949
- PMC
- PMC6492660
- OpenAlex
- W2743308848
- Cited by
- 42
- References
- 65
- Citations by year
- 2026: 5 · 2025: 4 · 2024: 5 · 2023: 4 · 2022: 7 · 2021: 4 · 2020: 3 · 2019: 5 · 2018: 4 · 2017: 1
- FWCI
- 2.63
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- CNS Neuroscience & Therapeutics (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Barrow Neurological Foundation
- National Natural Science Foundation of China (81671050)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Keywords
- APOE ε4, hippocampus, dendritic morphology, dendritic spines, synaptic function, CA1 neurons, CA3-CA1 synapses, long-term potentiation, paired-pulse facilitation, theta oscillations, carbachol, Alzheimer's disease risk, learning and memory impairment, young adult mice
- MeSH terms
- Animals, Dendrites, Disease Models, Animal, Electric Stimulation, Hippocampus, Humans, Mice, Transgenic, Nerve Net, Neurons, Synapses, Synaptic Vesicles, Statistics, Nonparametric, Excitatory Postsynaptic Potentials, Dendritic Spines, Mice, Apolipoprotein E3, Apolipoprotein E4, Biophysical Phenomena, In Vitro Techniques
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