Reduced Spine Density in Specific Regions of CA1 Pyramidal Neurons in Two Transgenic Mouse Models of Alzheimer's Disease
Open accessAbstract
One major hallmark of Alzheimer's disease (AD) is the massive loss of synapses that occurs at an early clinical stage of the disease. In this study, we characterize alterations in spine density and the expression of synapse-associated immediate early gene Arc (activity-regulated cytoskeleton-associated protein) in the hippocampal CA1 regions of two different amyloid precursor protein (APP) transgenic mouse lines before plaque development and their connection to performance in hippocampus-dependent memory tests. The density of mushroom-type spines was reduced by 34% in the basal dendrites proximal to the soma of CA1 pyramidal neurons in 5.5-month-old Tg2576 mice, carrying the Swedish mutation, compared with wild-type littermates. A similar reduction of 42% was confirmed in the same region of 8-month-old APP/Lo mice, carrying the London mutation. In this strain, the reduction extended to the distal dendritic spines (28%), although no differences were found in apical dendrites in either transgenic mouse line. Both transgenic mice lines presented a significant increase in Arc protein expression in CA1 compared with controls, suggesting rather an overactivity and increased spine turnover that was supported by a significant decrease in number of somatostatin-immunopositive inhibitory interneurons in the stratum oriens of CA1. Behaviorally, the transgenic mice showed decrease freezing in the fear contextual conditioning test and impairment in spatial memory assessed by Morris water maze test. These data indicate that cognitive impairment in APP transgenic mice is correlated with impairment of synaptic connectivity in hippocampal CA1, probably attributable to loss of inhibitory interneurons and subsequent hyperactivity.
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Decreases in both thin and mushroom spine types have been reported in animal models of cognitive decline.
“Decreases in both spine types have been reported in animal models of cognitive decline [54], [55].”
From Arf4 Determines Dentate Gyrus-Mediated Pattern Separation by Regulating Dendritic Spine Development (2012) · cites this paper as [55]
The ‘Density of synaptic spines in CA1 of the hippocampus’ section reports reduced mushroom-like spine density in two transgenic mouse lines with cognitive deficits. The paper counted only mushroom-like spines, so it does not support a decrease in thin spines. (LLM, conf=0.90)
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- Authors
- Perez-Cruz, C., Nolte, M. W., van Gaalen, M. M., Rustay, N. R., Termont, A., Tanghe, A., Kirchhoff, F., & Ebert, U.
- Affiliations
- Abbott (Germany) (DE)
- Max Planck Society (DE)
- Corresponding author
- Ebert, Ulrich
- ORCID
- Kirchhoff, Frank
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2011-03-09
- Volume
- 31
- Issue
- 10
- Pages
- 3926-3934
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC6622797
- OpenAlex
- W1982747275
- Cited by
- 172
- References
- 8
- Citations by year
- 2026: 2 · 2025: 7 · 2024: 10 · 2023: 4 · 2022: 10 · 2021: 10 · 2020: 13 · 2019: 10 · 2018: 10 · 2017: 13 · 2016: 7 · 2015: 16 · 2014: 15 · 2013: 12 · 2012: 26
- FWCI
- 12.38
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Max Planck Institute for Plasma Physics (submittedVersion)
- MPG.PuRe (Max Planck Society) (submittedVersion)
- 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
- Alzheimer's disease, dendritic spine density, CA1 pyramidal neurons, Arc expression, amyloid precursor protein transgenic mice, Tg2576 mice, Swedish mutation, mushroom spines, inhibitory interneurons, somatostatin, hippocampal hyperactivity, synaptic loss, spatial memory impairment
- MeSH terms
- Alzheimer Disease, Analysis of Variance, Animals, Conditioning, Classical, Cytoskeletal Proteins, Disease Models, Animal, Fear, Immunohistochemistry, Mice, Transgenic, Nerve Tissue Proteins, Somatostatin, Pyramidal Cells, Freezing Reaction, Cataleptic, Dendritic Spines, Mice, CA1 Region, Hippocampal
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