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Impaired Cognitive Flexibility Induced by Chronic Cerebral Hypoperfusion in the 5XFAD Transgenic Mouse Model of Mixed Dementia.
- Source :
- Journals of Gerontology Series A: Biological Sciences & Medical Sciences; Jul2021, Vol. 76 Issue 7, p1169-1178, 10p
- Publication Year :
- 2021
-
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. [ABSTRACT FROM AUTHOR]
- Subjects :
- LABORATORY mice
COGNITIVE flexibility
TRANSGENIC mice
ARTERIAL occlusions
ANIMAL disease models
CAROTID artery
BIOLOGICAL models
RESEARCH
ALZHEIMER'S disease
CAROTID artery stenosis
ANIMAL experimentation
RESEARCH methodology
EVALUATION research
COMPARATIVE studies
DEMENTIA
CEREBRAL ischemia
MICE
DISEASE complications
Subjects
Details
- Language :
- English
- ISSN :
- 10795006
- Volume :
- 76
- Issue :
- 7
- Database :
- Complementary Index
- Journal :
- Journals of Gerontology Series A: Biological Sciences & Medical Sciences
- Publication Type :
- Academic Journal
- Accession number :
- 151011378
- Full Text :
- https://doi.org/10.1093/gerona/glab075