Behavioural, physiological and morphological analysis of a line of apolipoprotein E knockout mouse
Abstract
Using apolipoprotein E knockout mice derived from the Maeda source [Piedrahita J. A. et al. (1992) Proc. natn. Acad Sci. US.A. 89, 4471 4475], we have studied the influence of apolipoprotein E gene deletion on normal CNS function by neurological tests and water maze learning, hippocampal ultrastructure assessed by quantitative immunocytochemistry and electron microscopy, CNS plasticity, i.e. hippocampal long-term potentiation and amygdaloid kindling, and CNS repair, i.e. synaptic recovery in the hippocampus following deafferentation. In each study there was little difference between the apolipoprotein E knockout mice and wild-type controls of similar age and genetic background. Apolipoprotein E knockout mice aged eight months demonstrated accurate spatial learning and normal neurological function. Synaptophysin and microtubule-associated protein 2 immunohistochemistry and electron microscopic analysis of these animals revealed that the hippocampal synaptic and dendritic densities were similar between genotypes. The induction and maintenance of kindled seizures and hippocampal long-term potentiation were indistinguishable between groups. Finally, unilateral entorhinal cortex lesions produced a marked loss of hippocampal synaptophysin immunoreactivity in both groups and a marked up-regulation of apolipoprotein E in the wild-type group. Both apolipoprotein E knockout and wild-type groups showed immunohistochemical evidence of reactive synaptogenesis, although the apolipoprotein…
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Whether apoE-containing lipoproteins play a major role in supporting synaptogenesis and maintenance of synaptic connections in vivo in the uninjured brain has not yet been proven.
“Whether apoE-containing lipoproteins play a major role in supporting synaptogenesis and maintenance of synaptic connections in vivo in the uninjured brain has not yet been proven, as several studies have shown that the brain of apoE knock-out mice for the most part appears normal in the absence of injury (Anderson et al., 1998; Fagan et al., 1998).”
From The role of apolipoprotein E in Alzheimer's disease (2009) · cites this paper as Anderson et al., 1998
Cites
Plump, A. S., Smith, J. D., Hayek, T., Aalto-Setälä, K., Walsh, A., Verstuyft, J. G., Rubin, E. M., & Breslow, J. L. (1992) · Cell · doi:10.1016/0092-8674(92)90362-g · Cited by 2,263 · see citing works
Apolipoprotein E: Structure-Function Relationships
Weisgraber, K. H. (1994) · Advances in Protein Chemistry · doi:10.1016/s0065-3233(08)60642-7 · Cited by 830 · see citing works
Owen, E. H., Logue, S. F., Rasmussen, D. L., & Wehner, J. M. (1997) · Neuroscience · doi:10.1016/s0306-4522(97)00165-6 · Cited by 347 · see citing works
May, P. C., Lampert-Etchells, M., Johnson, S. A., Poirier, J., Masters, J. N., & Finch, C. E. (1990) · Neuron · doi:10.1016/0896-6273(90)90342-d · Cited by 339 · see citing works
Normal spatial learning despite regional inhibition of LTP in mice lacking Thy-1
Nosten-Bertrand, M., Errington, M. L., Murphy, K. P. S. J., Tokugawa, Y., Barboni, E., Kozlova, E., Michalovich, D., Morris, R. G. M., Silver, J., Stewart, C. L., et al. (1996) · Nature · doi:10.1038/379826a0 · Cited by 232 · see citing works
Self-citationXu, P.-T., Schmechel, D., Rothrock-Christian, T., Burkhart, D. S., Qiu, H.-L., Popko, B., Sullivan, P., Maeda, N., Saunders, A. M., Roses, A. D., et al. (1996) · Neurobiology of Disease · doi:10.1006/nbdi.1996.0023 · Cited by 178 · see citing works
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The role of apolipoprotein E in Alzheimer's disease
Kim, J., Basak, J. M., & Holtzman, D. M. (2009) · Neuron · doi:10.1016/j.neuron.2009.06.026 · Cited by 1,661 · see citing works
Apolipoprotein E and Apolipoprotein E Receptors: Normal Biology and Roles in Alzheimer Disease
Holtzman, D. M., Herz, J., & Bu, G. (2012) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a006312 · Cited by 782 · see citing works
Liu, L., MacKenzie, K. R., Putluri, N., Maletić-Savatić, M., & Bellen, H. J. (2017) · Cell Metabolism · doi:10.1016/j.cmet.2017.08.024 · Cited by 556 · see citing works
Reelin, lipoprotein receptors and synaptic plasticity
Herz, J., & Chen, Y. (2006) · Nature Reviews Neuroscience · doi:10.1038/nrn2009 · Cited by 524 · see citing works
Cholesterol metabolism in neurons and astrocytes
Pfrieger, F. W., & Ungerer, N. (2011) · Progress in Lipid Research · doi:10.1016/j.plipres.2011.06.002 · Cited by 500 · see citing works
HDL and cholesterol handling in the brain
Vitali, C., Wellington, C. L., & Calabresi, L. (2014) · Cardiovascular Research · doi:10.1093/cvr/cvu148 · Cited by 254 · see citing works
Huynh, T.-P. V., Davis, A. A., Ulrich, J. D., & Holtzman, D. M. (2017) · Journal of Lipid Research · doi:10.1194/jlr.r075481 · Cited by 210 · see citing works
Apolipoprotein E and cholesterol in aging and disease in the brain
de Chaves, E. P., Narayanaswami, V., Christoffersen, C., & Nielsen, L. B. (2008) · Future Lipidology · doi:10.2217/17460875.3.5.505 · Cited by 164 · see citing works
Brain cholesterol in normal and pathological aging
Martin, M., Dotti, C. G., & Ledesma, M. D. (2010) · Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids · doi:10.1016/j.bbalip.2010.03.011 · Cited by 162 · see citing works
Hartman, R. E., Wozniak, D. F., Nardi, A., Olney, J. W., Sartorius, L., & Holtzman, D. M. (2001) · Experimental Neurology · doi:10.1006/exnr.2001.7715 · Cited by 157 · see citing works
Tzioras, M., Davies, C., Newman, A., Jackson, R., & Spires‐Jones, T. (2019) · Neuropathology and Applied Neurobiology · doi:10.1111/nan.12529 · Cited by 147 · see citing works
White, F., Nicoll, J. A. R., Roses, A. D., & Horsburgh, K. (2001) · Neurobiology of Disease · doi:10.1006/nbdi.2001.0401 · Cited by 128 · see citing works
Teter, B., Xu, P. ‐., Gilbert, J. R., Roses, A. D., Galasko, D., & Cole, G. M. (1999) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.1999.0732613.x · Cited by 88 · see citing works
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
Mulder, M., Blokland, A., van den Berg, D.-J., Schulten, H., Bakker, A. H. F., Terwel, D., Honig, W., de Kloet, E. R., Havekes, L. M., Steinbusch, H. W. M., et al. (2001) · Laboratory Investigation · doi:10.1038/labinvest.3780307 · Cited by 74 · see citing works
Hernandez Torres, L. D., Rezende, F., Peschke, E., Will, O., Hövener, J.-B., Spiecker, F., Özorhan, Ü., Lampe, J., Stölting, I., Aherrahrou, Z., et al. (2024) · Frontiers in Endocrinology · doi:10.3389/fendo.2024.1338458 · Cited by 8 · see citing works
- Authors
- Anderson, R., Barnes, J. C., Bliss, T. V. P., Cain, D. P., Cambon, K., Davies, H. A., Errington, M. L., Fellows, L. A., Gray, R. A., Hoh, T., Stewart, M., Large, C. H., & Higgins, G. A.
- Affiliations
- National Institute for Medical Research (GB)
- Western University (CA)
- The Open University (GB)
- Corresponding author
- Higgins, G.A.
- Venue
- Neuroscience
- Publisher
- Elsevier BV
- Published
- 1998-03
- Volume
- 85
- Issue
- 1
- Pages
- 93-110
- ISSN
- 0306-4522 (ISSN-L)
- OpenAlex
- W1977086524
- Cited by
- 119
- References
- 6
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 1 · 2023: 1 · 2022: 1 · 2021: 3 · 2020: 2 · 2018: 2 · 2017: 6 · 2016: 2 · 2015: 1 · 2014: 3 · 2013: 6 · 2012: 4
- FWCI
- 5.11
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- 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 › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- apolipoprotein E, knockout mice, hippocampus, synaptic plasticity, long-term potentiation, kindling, deafferentation, synaptic recovery, entorhinal cortex lesion, synaptophysin, MAP2, hippocampal ultrastructure, spatial learning, CNS repair
- MeSH terms
- Animals, Apolipoproteins E, Behavior, Animal, Electrophysiology, Hippocampus, Immunohistochemistry, Kindling, Neurologic, Microtubule-Associated Proteins, Neurons, Synapses, Synaptophysin, Mice, Knockout, Entorhinal Cortex, Dentate Gyrus, GAP-43 Protein, Mice
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