Research Paper Volume 11, Issue 16 pp 5924—5942

Cognitive impairment in heart failure is associated with altered Wnt signaling in the hippocampus

Camilo Toledo1,4, , Claudia Lucero1, , David C. Andrade1,3, , Hugo S. Díaz1, , Karla G. Schwarz1, , Katherin V. Pereyra1, , Alexis Arce-Álvarez1, , Nicolás A. López1, , Milka Martinez2, , Nibaldo C. Inestrosa2,4, , Rodrigo Del Rio1,2,4, ,

  • 1 Laboratory of Cardiorespiratory Control, Department of Physiology, Pontificia Universidad Católica de Chile, Santiago, Chile
  • 2 Center for Aging and Regeneration (CARE-UC), Pontificia Universidad Católica de Chile, Santiago, Chile
  • 3 Centro de Investigación en Fisiología del Ejercicio, Universidad Mayor, Santiago, Chile
  • 4 Centro de Excelencia de Biomedicina en Magallanes (CEBIMA), Universidad de Magallanes, Punta Arenas, Chile

Received: February 22, 2019       Accepted: July 31, 2019       Published: August 25, 2019
How to Cite

Copyright © 2019 Toledo et al. This is an open-access article distributed under the terms of the Creative Commons Attribution (CC BY 3.0) License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


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.


HF: heart failure; CI: cognitive impairments; EF: ejection fraction; HFrEF: heart failure with reduced ejection fraction; HFpEF: heart failure with preserved ejection fraction; A-V: arteriovenous; EDV: end-diastolic volume; SV: stroke volume; ESD: end-systolic diameter; EDD: end-diastolic diameter; ESV: end-systolic volume; SBP: systolic blood pressure; DBP: diastolic blood pressure; PP: pulse pressure; HR: heart rate; MWM: Morris Water Maze; MF: memory flexibility; GSK-3β: glycogen synthase kinase- 3β; β-Ars: β adrenergic receptors; NE: Norepinephrine.