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Updated: Jan 20, 2026
Modeling Paracrine Noncanonical Wnt Signaling In Vitro
Published on: December 10, 2021
Cognitive impairment in heart failure is associated with altered Wnt signaling in the hippocampus
Camilo Toledo1,2, Claudia Lucero1, David C Andrade1,3
1Laboratory of Cardiorespiratory Control, Department of Physiology, Pontificia Universidad Católica de Chile, Santiago, Chile.
Insights
Heart failure (HF) in elderly patients often leads to cognitive impairment (CI). This study found HF rats showed memory loss and impaired learning, linked to Wnt/β-catenin pathway dysfunction in the brain.
Area of Science:
- Neuroscience
- Cardiovascular Science
- Aging Research
Background:
- Age is the primary risk factor for cardiovascular disease mortality.
- Heart failure (HF) is prevalent in the elderly and frequently associated with cognitive impairment (CI).
- While reduced brain oxygen supply is a known cause of CI in HF, mechanisms in HF without altered cerebral blood flow remain unclear.
Purpose of the Study:
- To investigate learning and memory functions in a rodent model of HF without changes in cerebral blood flow.
- To explore the underlying pathophysiological mechanisms of CI in this specific HF subset.
Main Methods:
- Utilized a rodent model of heart failure (HF) exhibiting normal brain perfusion.
- Assessed learning and memory performance in HF rats.
- Analyzed Wnt/β-catenin signaling pathway elements in the hippocampus of HF rats.
Main Results:
- HF rats demonstrated significant learning impairments and memory deficits.
- HF rats exhibited reduced levels of Wnt/β-catenin signaling downstream components in the hippocampus.
- These findings suggest a link between HF, CI, and Wnt/β-catenin pathway alterations.
Conclusions:
- Cognitive impairment in HF rats, even without altered cerebral blood flow, is associated with Wnt/β-catenin signaling pathway dysfunction.
- Further research is needed to elucidate the precise mechanisms linking Wnt/β-catenin signaling alterations to CI development in HF.
Abstract:
Age represents the highest risk factor for death due to cardiovascular disease. Heart failure (HF) is the most common cardiovascular disease in elder population and it is associated with cognitive impairment (CI), diminishing learning and memory process affecting life quality and mortality in these patients. In HF, CI has been associated with inadequate O2 supply to the brain; however, an important subset of HF patients displays CI with almost no alteration in cerebral blood flow. Importantly, nothing is known about the pathophysiological mechanisms underpinning CI in HF with no change in brain tissue perfusion. Here, we aimed to study memory performance and learning function in a rodent model of HF that shows no change in blood flow going to the brain. We found that HF rats presented learning impairments and memory loss. In addition, HF rats displayed a decreased level of Wnt/β-catenin signaling downstream elements in the hippocampus, one pathway implicated largely in aging diseases. Taken together, our results suggest that in HF rats CI is associated with dysfunction of the Wnt/β-catenin signaling pathway. The mechanisms involved in the alterations of Wnt/β-catenin signaling in HF and its contribution to the development/maintenance of CI deserves future investigations.
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