Impairments in remote memory stabilization precede hippocampal synaptic and cognitive failures in 5XFAD Alzheimer mouse model
Open accessAbstract
Although animal models of Alzheimer's disease (AD) recapitulate beta-amyloid-dependent hippocampal synaptic and cognitive dysfunctions, it is poorly understood how cortex-dependent remote memory stabilization following initial hippocampal coding is affected. Here, we systematically analyzed biophysical and behavioral phenotypes, including remote memory functions, of 5XFAD APP/PS1 transgenic mice containing five familial AD mutations. We found that 5XFAD mice show hippocampal dysfunctions as observed by reduced levels of baseline transmission and long-term potentiation at Schaffer collateral-CA1 synapses. Hippocampus-dependent memory tested 1 day after contextual fear conditioning was also impaired age-dependently in 5XFAD mice, as correlated with the onset of hippocampal synaptic failures. Importantly, remote memory stabilization during 30 days after training significantly declined in 5XFAD mice at time well before the onset of hippocampal dysfunctions. Our results indicate that 5XFAD mice provide a useful model system to investigate the mechanisms and therapeutic interventions for multiple synaptic and memory dysfunctions associated with AD.
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5xFAD mice show hippocampus-dependent memory deficits at 4-6 months of age compared to wildtype littermates, detectable by contextual fear conditioning.
“5xFAD mice show hippocampus-dependent memory deficits at 4–6 months of age compared to wildtype littermates which can be detected by a contextual fear conditioning paradigm [39].”
From PCSK9 acts as a key regulator of Aβ clearance across the blood–brain barrier (2022) · cites this paper as [39]
The Results section ('Impairments of hippocampal memory formation in 5XFAD mice') reports significantly less freezing in 6-month-old 5XFAD mice than in wild-type littermates one day after contextual fear conditioning. The paper does not establish deficits across the stated 4–6-month range: mice younger than 4 months performed comparably to controls, and a 4-month-old group is not reported. (LLM, conf=0.86)
Experimental — accuracy not yet measuredFemale 5xFAD mice display considerable Aβ1-42 burden, distinct plaque pathology and impaired cognitive capacities already at 6 months of age.
“Female 5xFAD mice display a considerable Aβ1–42 burden, distinct plaque pathology and impaired cognitive capacities already at 6 months of age [38, 39]”
From PCSK9 acts as a key regulator of Aβ clearance across the blood–brain barrier (2022) · cites this paper as [39]
The Introduction reports accelerated Aβ42 production and massive amyloid deposition in 6-month-old 5XFAD mice. The Results section on hippocampal memory formation reports impaired contextual fear memory at that age. Neither passage, nor the Mouse lines methods, identifies the mice as female, so the sex-specific claim is not established by this paper. (LLM, conf=0.87)
Experimental — accuracy not yet measuredTargeting peripheral PCSK9 in 5xFAD mice preserves hippocampus-dependent learning capacities to a level of control-treated wildtype littermates.
“targeting peripheral PCSK9 in 5xFAD mice preserves hippocampus-dependent learning capacities [39] to a level of control-treated wildtype littermates (Fig. 6A).”
From PCSK9 acts as a key regulator of Aβ clearance across the blood–brain barrier (2022) · cites this paper as [39]
Previous reports have found that 5XFAD mice do not have short term reconsolidation deficits.
“Since previous reports have found that 5XFAD mice do not have short term reconsolidation deficits, we quantified remote memory stabilization over 14 days using a fear conditioning assay optimized by Kimura et al. for the 5XFD model31.”
From Neuronally-directed effects of RXR activation in a mouse model of Alzheimer’s disease (2017) · cites this paper as [31]
5XFAD mice exhibit normal reconsolidation of contextual fear memory.
“As previously reported, 5XFAD mice exhibit normal reconsolidation of contextual fear memory3161.”
From Neuronally-directed effects of RXR activation in a mouse model of Alzheimer’s disease (2017) · cites this paper as [31]
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- Authors
- Kimura, R., & Ohno, M.
- Affiliations
- New York University (US)
- Corresponding author
- Ohno, Masuo
- ORCID
- Ohno, Masuo
- Venue
- Neurobiology of Disease
- Publisher
- Elsevier BV
- Published
- 2009-02
- Volume
- 33
- Issue
- 2
- Pages
- 229-235
- ISSN
- 0969-9961 (ISSN-L)
- PMC
- PMC2741400
- OpenAlex
- W2166267133
- Cited by
- 333
- References
- 52
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- FWCI
- 2.93
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- Locations
- Neurobiology of Disease (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- National Institute of Mental Health (R01 MH067251)
- Alzheimer's Association (IIRG-08-91231)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- Alzheimer's disease, 5xFAD mice, APP/PS1 mice, hippocampus, long-term potentiation, Schaffer collateral-CA1 synapses, synaptic dysfunction, contextual fear conditioning, amyloid-beta, cognitive impairment, memory consolidation
- MeSH terms
- Age Factors, Alzheimer Disease, Animals, Conditioning, Psychological, Disease Models, Animal, Extinction, Psychological, Fear, Hippocampus, Humans, Memory, Mice, Transgenic, Mutation, Synaptic Transmission, Receptors, Cell Surface, Amyloid beta-Protein Precursor, Long-Term Potentiation, Excitatory Postsynaptic Potentials, Mice, Presenilin-1, Protease Nexins
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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