Age-dependent enhancement of hippocampal long-term potentiation in knock-in mice expressing human apolipoprotein E4 instead of mouse apolipoprotein E.
Abstract
Human apolipoprotein E (apoE) comprises three isoforms, apoE2, apoE3 and apoE4, and apoE4 has been reported as a risk factor of Alzheimer's disease (AD). One of the clinical symptoms of AD is disorder of memory that has been suggested to be related with synaptic plasticity such as long-term potentiation (LTP). Here, we show the enhancement of hippocampal LTP at younger age in knock-in mice lacking mouse apoE, but instead expressing human apoE4. The enhancement of LTP in apoE4 knock-in mice is age-dependent, and it disappears in adult apoE4 knock-in mice. In apoE3 knock-in mice LTP is unaltered, thus human apoE4, but not apoE3, specifically modulates synaptic plasticity at younger age. Since basal synaptic transmission and distribution of glutamate receptors, as well as presynaptic functions, are intact in apoE4 knock-in mice, postsynaptic functional modification of LTP through lipid homeostasis is suggested. ApoE4 knock-in mice would be a useful animal model of human apoE4 carriers, and our finding that LTP is enhanced in younger apoE4 knock-in mice is in accord with the previous report showing higher intelligence in young human apoE4 carriers.
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Young apoE4 mice had enhanced LTP.
“another study showed young apoE4 mice had enhanced LTP (Kitamura et al., 2004).”
From Apolipoprotein E in Synaptic Plasticity and Alzheimer’s Disease: Potential Cellular and Molecular Mechanisms (2014) · cites this paper as Kitamura et al., 2004
Cites
Cholinergic systems and long-term potentiation in memory-impaired apolipoprotein E-deficient mice
Krzywkowski, P., Ghribi, O., Gagné, J., Chabot, C., Kar, S., Rochford, J., Massicotte, G., & Poirier, J. (1999) · Neuroscience · doi:10.1016/s0306-4522(99)00061-5 · Cited by 74 · see citing works
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Reelin, lipoprotein receptors and synaptic plasticity
Herz, J., & Chen, Y. (2006) · Nature Reviews Neuroscience · doi:10.1038/nrn2009 · Cited by 524 · see citing works
Kim, J., Yoon, H., Basak, J., & Kim, J. (2014) · Molecules and Cells · doi:10.14348/molcells.2014.0248 · Cited by 141 · see citing works
“Cells http://molcells.org Transgene Promoter Phenotypes Age (months) Note REF Human apoE2,E3, E4 KI and apoE KO endogenous LTP magnitude; WT and apoE3 > apoE KO and apoE2 > apoE4 2-4 (Trommer et al., 2004) Human apoE3,E4 KI endogenous Hippocampal LTP was enhanced at a younger age in apoE 4 KI but not in apoE3 KI 8 wee…”
BackgroundResultInfluentialApoE isoform-dependent changes in hippocampal synaptic function
Korwek, K. M., Trotter, J. H., LaDu, M. J., Sullivan, P. M., & Weeber, E. J. (2009) · Molecular Neurodegeneration · doi:10.1186/1750-1326-4-21 · Cited by 89 · see citing works
Mak, E., Gabel, S., Mirette, H., Su, L., Williams, G. B., Waldman, A., Wells, K., Ritchie, K., Ritchie, C., & O’Brien, J. (2017) · Ageing Research Reviews · doi:10.1016/j.arr.2016.10.001 · Cited by 71 · see citing works
Koch, G., Di Lorenzo, F., Loizzo, S., Motta, C., Travaglione, S., Baiula, M., Rimondini, R., Ponzo, V., Bonnì, S., Toniolo, S., et al. (2017) · Scientific Reports · doi:10.1038/s41598-017-14204-3 · Cited by 64 · see citing works
Sun, G., He, Y., Ma, X. K., Li, S., Chen, D., Gao, M., Qiu, S., Yin, J., Shi, J., & Wu, J. (2017) · CNS Neuroscience & Therapeutics · doi:10.1111/cns.12720 · Cited by 42 · see citing works
O'Dwyer, L., Lamberton, F., Matura, S., Scheibe, M., Miller, J., Rujescu, D., Prvulovic, D., & Hampel, H. (2012) · PLoS ONE · doi:10.1371/journal.pone.0036024 · Cited by 34 · see citing works
Opposing Roles of apolipoprotein E in aging and neurodegeneration
Hudry, E., Klickstein, J., Cannavo, C., Jackson, R., Muzikansky, A., Gandhi, S., Urick, D., Sargent, T., Wrobleski, L., Roe, A. D., et al. (2019) · Life Science Alliance · doi:10.26508/lsa.201900325 · Cited by 30 · see citing works
- Authors
- Kitamura, H. W., Hamanaka, H., Watanabe, M., Wada, K., Yamazaki, C., Fujita, S. C., Manabe, T., & Nukina, N.
- Affiliations
- RIKEN (JP)
- Hokkaido University (JP)
- Institute of Medical Science, The University of Tokyo (JP)
- Corresponding author
- Manabe, Toshiya
- Nukina, Nobuyuki
- Venue
- Neuroscience Letters
- Publisher
- Elsevier BV
- Published
- 2004-10
- Volume
- 369
- Issue
- 3
- Pages
- 173-178
- ISSN
- 0304-3940 (ISSN-L)
- OpenAlex
- W2079428657
- Cited by
- 35
- References
- 1
- Citations by year
- 2026: 1 · 2023: 1 · 2022: 3 · 2021: 2 · 2020: 1 · 2019: 2 · 2017: 4 · 2016: 2 · 2015: 1 · 2014: 2 · 2013: 2 · 2012: 1
- FWCI
- 0.59
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Neuroscience Letters (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Ministry of Education, Culture, Sports, Science and Technology
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Keywords
- APOE ε4, apolipoprotein E isoforms, long-term potentiation, hippocampus, synaptic plasticity, Alzheimer's disease risk, lipid homeostasis, postsynaptic function, memory
- MeSH terms
- Aging, Animals, Apolipoproteins E, Dose-Response Relationship, Radiation, Electric Stimulation, Hippocampus, Humans, Immunohistochemistry, Mice, Inbred C57BL, Mice, Mutant Strains, Synaptic Transmission, 2-Amino-5-phosphonovalerate, Receptors, N-Methyl-D-Aspartate, Long-Term Potentiation, Receptors, AMPA, Excitatory Amino Acid Antagonists, 6-Cyano-7-nitroquinoxaline-2,3-dione, Excitatory Postsynaptic Potentials, Mice, Apolipoprotein E4, In Vitro Techniques
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