ArticleThe journals of gerontology. Series A, Biological sciences and medical sciences2021
Impaired Cognitive Flexibility Induced by Chronic Cerebral Hypoperfusion in the 5XFAD Transgenic Mouse Model of Mixed Dementia.
Article in The journals of gerontology. Series A, Biological sciences and medical sciences, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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8 citing papers in PubMed, 15 citations in OpenAlex.
- Age-dependent vulnerability to spatial memory interference in APP/PS1 mice.Frontiers in aging neuroscience · 2026Article
- A Novel Mouse Model of Mixed Dementia Using Chronic Cerebral Hypoperfusion Induced by Bilateral Carotid Artery Stenosis.Journal of Korean medical science · 2025Article
- Differences in Learning Strategy Selection and Object Location Memory Impairments in APP/PS1 Mice.Experimental neurobiology · 2025Article
- A new method for community-based intelligent screening of early Alzheimer's disease populations based on digital biomarkers of the writing process.Frontiers in computational neuroscience · 2025Article
- Temporal and region-specific tau hyperphosphorylation in the medulla and forebrain coincides with development of functional changes in male obese Zucker rats.Journal of neurophysiology · 2024Article
- Mumefural Improves Recognition Memory and Alters ERK-CREB-BDNF Signaling in a Mouse Model of Chronic Cerebral Hypoperfusion.Nutrients · 2023Article
- Enriched environment attenuates hippocampal theta and gamma rhythms dysfunction in chronic cerebral hypoperfusion via improving imbalanced neural afferent levels.Frontiers in cellular neuroscience · 2023Article
- Effects of α5 GABACNS neuroscience & therapeutics · 2022Article
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Authors and funding
4 authors at 2 institutions in 1 country.
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No grant is acknowledged in the PubMed record.
Abstract
Cerebrovascular lesions are widely prevalent in patients with Alzheimer's disease (AD), but their relationship to the pathophysiology of AD remains poorly understood. An improved understanding of the interaction of cerebrovascular damage with AD is crucial for the development of therapeutic approaches. Herein, we investigated the effects of chronic cerebral hypoperfusion (CCH) in a 5XFAD transgenic (Tg) mouse model of AD. We established CCH conditions in both Tg and non-Tg mice by inducing unilateral common carotid artery occlusion (UCCAO). Cognitive performance in mice was evaluated, and their brain tissue was examined for amyloid-beta (Aβ) pathology to elucidate possible mechanisms. We found that UCCAO-operated Tg mice showed impaired cognitive flexibility in the reversal phase of the hidden-platform water maze task compared to sham-operated Tg mice. Interestingly, UCCAO-operated Tg mice used fewer spatial cognitive strategies than sham-operated Tg mice during reversal learning. These cognitive deficits were accompanied by increased Aβ plaque burden and Aβ42 levels in the hippocampus and prefrontal cortex, 2 regions that play essential roles in the regulation of cognitive flexibility. Furthermore, changes in cognitive flexibility are strongly correlated with the expression levels of enzymes related to Aβ clearance, such as neprilysin and insulin-degrading enzymes. These findings suggest that, in 5XFAD mice, impaired cognitive flexibility is related to CCH, and that Aβ clearance might be involved in this process.
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