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A Comprehensive Behavioral Test Battery to Assess Learning and Memory in 129S6/Tg2576 Mice
Open accessAbstract
Transgenic Tg2576 mice overexpressing human amyloid precursor protein (hAPP) are a widely used Alzheimer's disease (AD) mouse model to evaluate treatment effects on amyloid beta (Aβ) pathology and cognition. Tg2576 mice on a B6;SJL background strain carry a recessive rd1 mutation that leads to early retinal degeneration and visual impairment in homozygous carriers. This can impair performance in behavioral tests that rely on visual cues, and thus, affect study results. Therefore, B6;SJL/Tg2576 mice were systematically backcrossed with 129S6/SvEvTac mice resulting in 129S6/Tg2576 mice that lack the rd1 mutation. 129S6/Tg2576 mice do not develop retinal degeneration but still show Aβ accumulation in the brain that is comparable to the original B6;SJL/Tg2576 mouse. However, comprehensive studies on cognitive decline in 129S6/Tg2576 mice are limited. In this study, we used two dementia mouse models on a 129S6 background--scopolamine-treated 129S6/SvEvTac mice (3-5 month-old) and transgenic 129S6/Tg2576 mice (11-13 month-old)-to establish a behavioral test battery for assessing learning and memory. The test battery consisted of five tests to evaluate different aspects of cognitive impairment: a Y-Maze forced alternation task, a novel object recognition test, the Morris water maze, the radial arm water maze, and a Y-maze spontaneous alternation task. We first established this behavioral test battery with the scopolamine-induced dementia model using 129S6/SvEvTac mice and then evaluated 129S6/Tg2576 mice using the same testing protocol. Both models showed distinctive patterns of cognitive impairment. Together, the non-invasive behavioral test battery presented here allows detecting cognitive impairment in scopolamine-treated 129S6/SvEvTac mice and in transgenic 129S6/Tg2576 mice. Due to the modular nature of this test battery, more behavioral tests, e.g. invasive assays to gain additional cognitive information, can easily be added.
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“For behavioral tests, exclusion criteria were pre-established following published guidance 71,79,80.”
From Exercise hormone irisin is a critical regulator of cognitive function (2021) · cites this paper as [71]
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Metadata
- Authors
- Wolf, A., Bauer, B., Abner, E. L., Ashkenazy-Frolinger, T., & Hartz, A. M. S.
- Affiliations
- University of Minnesota, Duluth (US)
- University of Kentucky (US)
- Corresponding author
- Hartz, Anika M. S.
- Venue
- PLOS ONE
- Publisher
- Public Library of Science (PLoS)
- Published
- 2016-01-25
- Volume
- 11
- Issue
- 1
- Pages
- e0147733
- ISSN
- 1932-6203 (ISSN-L)
- PMC
- PMC4726499
- OpenAlex
- W2426168356
- Cited by
- 281
- References
- 89
- Citations by year
- 2026: 16 · 2025: 20 · 2024: 28 · 2023: 37 · 2022: 30 · 2021: 33 · 2020: 37 · 2019: 28 · 2018: 40 · 2017: 6 · 2016: 6
- FWCI
- 21.46
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- PLoS ONE (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- UKnowledge (University of Kentucky) (submittedVersion, cc-by)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Figshare (submittedVersion, cc-by)
- Funders
- University of Kentucky (P30 AG028383, AG028383)
- National Institute on Aging (AG-028383, P30AG028383, R01AG039621)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Keywords
- mouse models of Alzheimer's disease, amyloid precursor protein overexpression, retinal degeneration, scopolamine-induced dementia, cognitive impairment, learning and memory, novel object recognition, Morris water maze, radial arm water maze, spontaneous alternation, amyloid-beta pathology
- MeSH terms
- Animals, Behavior, Animal, Male, Memory, Mice, Transgenic, Maze Learning, Mice
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