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January 23, 2020Open Access

Administration of the HDAC inhibitor Vorinostat ameliorated memory impairment and partially restored physiological hippocampal gene expression in a mouse model of heart failure.

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Why the study?

Cognitive dysfunction is a severe burden in heart failure patients, but the underlying molecular mechanisms linking the two conditions and corresponding therapeutic strategies were unknown.

Does Vorinostat improve memory function and restore hippocampal gene expression in a mouse model of heart failure?

Population

Mice

Design

Preclinical animal model study

Key result

Administration of the HDAC inhibitor Vorinostat ameliorated memory impairment and partially restored physiological hippocampal gene expression in a mouse model of heart failure.

Authors

RIRezaul IslamDLDawid LbikSSSadman Sakib

Discussion

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Member takes

Overview

May support HDAC inhibition for heart failure-related cognitive impairment; hypothesis-generating in mice and leaves open human translation.

Structured PICO

Does Vorinostat improve memory function and restore hippocampal gene expression in a mouse model of heart failure?

P
Population
29 3-month-old CamkIIδc TG mice and wild-type littermates used to model heart failure-induced cognitive impairment.
I
Intervention
Vorinostat (HDAC inhibitor) administered orally for 1 month starting at 2 months of age.
C
Comparator
Vehicle solution.
O
Outcome
Hippocampus-dependent spatial navigation-learning and memory retrieval (assessed via Barnes Maze) and hippocampal gene expression.surrogate

Heart failure induces cognitive impairment via epigenetic changes in hippocampal gene expression, which can be ameliorated by the HDAC inhibitor Vorinostat in a mouse model.

Limitations

  • Cannot exclude the possibility that improved memory function is mediated by other mechanisms
  • Vorinostat also acts on non-histone proteins

Cite This Study

Islam et al. (2020) studied Heart failure-induced memory impairment (n=29). Vorinostat vs. Vehicle was evaluated on Spatial reference memory (Barnes Maze escape latency). Administration of the HDAC inhibitor Vorinostat ameliorated memory impairment and partially restored physiological hippocampal gene expression in a mouse model of heart failure.

synapsesocial.com/papers/6a7063fcce524a4339c41fefhttps://doi.org/10.1101/2020.01.22.915637
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Also Consider

Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context:

  1. 1Epigenetic gene expression links heart failure to memory impairment2021 · 30 citations
  2. 2A Multi-Gene Synaptic Plasticity Array Identifies Candidate Molecular Underpinnings of Cognitive and Mood Deficits in Rats with Heart Failure2020
  3. 3Current opinion in cardiology, epigenetics of heart failure2026 · 4 citations
  4. 4Epigenetic factors of heart failure (review)2024
  5. 5Heart failure, cognition, and brain damage2021 · 23 citations