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Maintained synaptophysin immunoreactivity in Tg2576 transgenic mice during aging: correlations with cognitive impairment
Abstract
Regional loss of synapses, particularly within the neocortex and hippocampus, is characteristic of Alzheimer's Disease (AD) and strongly correlated with extent of cognitive impairment. The Tg2576 transgenic mouse model of AD develops Abeta-containing neuritic plaques by 10-16 months of age and shows cognitive impairment in several tasks. In the present study, synaptophysin immunoreactivity (SYN-IR; a marker for synaptic terminals) was evaluated in the neocortex and hippocampus of behaviorally-tested Tg2576 transgenic (Tg+) mice aged 3, 9, 14, and 19 months of age. In control non-transgenic (Tg-) mice, SYN-IR in both neocortex and hippocampus tended to decrease with age, while SYN-IR in Tg+ mice was maintained with age. Thus, 19M Tg+ mice exhibited significantly greater synaptophysin immunostaining compared to 19M Tg- mice in both inner and outer neocortical regions, as well as in the dentate gyrus' outer molecular layer and polymorphic layer. Over all four age groups collectively, outer cortical SYN-IR was also greater in Tg+ compared to Tg- mice. Multiple factors could be responsible for maintained SYN-IR in aged Tg+ mice, including compensatory changes in synaptic morphology and staining of dystrophic neuritics associated with Abeta deposition. For all animals combined (Tg+ and Tg-), as well as for aged 19M animals alone, hippocampal SYN-IR was correlated with impaired acquisition and spatial reference memory in the Morris water maze task, suggestive that elevated hippocamp…
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“These observations concur with previous data in Tg2576 mice (Takeuchi et al., 2000; King and Arendash, 2002) and APP23 mice (Boncristiano et al., 2005) showing no change in synaptophysin immunoreactivity up to 19 and 24 months of age, respectively.”
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Metadata
- Authors
- King, D. L., & Arendash, G. W.
- Affiliations
- University of South Florida (US)
- Corresponding author
- Arendash, Gary W.
- ORCID
- Arendash, Gary W.
- Venue
- Brain Research
- Publisher
- Elsevier BV
- Published
- 2002-02
- Volume
- 926
- Issue
- 1-2
- Pages
- 58-68
- ISSN
- 0006-8993 (ISSN-L)
- OpenAlex
- W2058970680
- Cited by
- 105
- References
- 50
- Citations by year
- 2024: 2 · 2023: 2 · 2022: 3 · 2021: 2 · 2020: 1 · 2018: 8 · 2017: 4 · 2016: 1 · 2015: 4 · 2014: 3 · 2013: 10 · 2012: 8
- FWCI
- 4.40
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Brain Research (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Keywords
- synaptophysin, Tg2576 mice, Alzheimer's disease, aging, synaptic loss, neocortex, hippocampus, amyloid-beta, neuritic plaques, spatial reference memory, visual agnosia, cognitive impairment, synaptic function
- MeSH terms
- Aging, Alzheimer Disease, Animals, Behavior, Animal, Cognition Disorders, Disease Models, Animal, Female, Hippocampus, Immunohistochemistry, Male, Mice, Inbred C57BL, Mice, Transgenic, Synapses, Amyloid beta-Peptides, Synaptophysin, Neocortex, Mice
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