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Published on: March 29, 2024
Epigenetic gene expression links heart failure to memory impairment
Md Rezaul Islam1, Dawid Lbik2, M Sadman Sakib1
1Department for Systems Medicine and Epigenetics, German Center for Neurodegenerative Diseases (DZNE), Göttingen, Germany.
Insights
Heart failure causes cognitive decline by altering hippocampal gene expression in mice. A drug promoting neuronal euchromatin formation reversed these memory impairments, suggesting new therapeutic targets.
Area of Science:
- Neuroscience
- Cardiology
- Molecular Biology
Background:
- Organ-centered medical approaches may not fully address complex conditions like heart failure.
- Cognitive dysfunction and increased dementia risk are significant burdens in heart failure patients.
- Molecular mechanisms linking heart failure to cognitive impairment remain largely unknown.
Purpose of the Study:
- To investigate the molecular mechanisms underlying cognitive dysfunction in heart failure.
- To explore the impact of heart failure on hippocampal gene expression and neuronal function.
- To identify potential therapeutic strategies for improving cognition in heart failure.
Main Methods:
- Utilized a mouse model of heart failure.
- Analyzed hippocampal gene expression changes.
- Assessed memory function in affected mice.
- Administered a drug promoting neuronal euchromatin formation.
Main Results:
- Heart failure induced specific changes in hippocampal gene expression, including increased cellular stress pathways.
- Observed loss of neuronal euchromatin and reduced expression of cognition-essential genes in the hippocampus.
- Mice with heart failure demonstrated impaired memory function.
- Drug administration ameliorated pathological changes and improved cognitive function.
Conclusions:
- Heart failure contributes to neuronal dysfunction and cognitive deficits through molecular alterations in the hippocampus.
- Targeting neuronal euchromatin formation presents a promising therapeutic avenue for cognitive defects in heart failure.
- This study provides crucial insights into the link between cardiac health and brain function.
Abstract:
In current clinical practice, care of diseased patients is often restricted to separated disciplines. However, such an organ-centered approach is not always suitable. For example, cognitive dysfunction is a severe burden in heart failure patients. Moreover, these patients have an increased risk for age-associated dementias. The underlying molecular mechanisms are presently unknown, and thus, corresponding therapeutic strategies to improve cognition in heart failure patients are missing. Using mice as model organisms, we show that heart failure leads to specific changes in hippocampal gene expression, a brain region intimately linked to cognition. These changes reflect increased cellular stress pathways which eventually lead to loss of neuronal euchromatin and reduced expression of a hippocampal gene cluster essential for cognition. Consequently, mice suffering from heart failure exhibit impaired memory function. These pathological changes are ameliorated via the administration of a drug that promotes neuronal euchromatin formation. Our study provides first insight to the molecular processes by which heart failure contributes to neuronal dysfunction and point to novel therapeutic avenues to treat cognitive defects in heart failure patients.
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