Epigenetic gene expression links heart failure to memory impairment
Open Access
- 20 January 2021
- journal article
- research article
- Published by Springer Science and Business Media LLC in EMBO Molecular Medicine
- Vol. 13 (3), e11900
- https://doi.org/10.15252/emmm.201911900
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.Funding Information
- Deutsche Forschungsgemeinschaft (EXC 2067/1 390729940, SFB1002, DFG Ka1269/13‐1)
This publication has 80 references indexed in Scilit:
- Cognitive impairment and self-care in heart failureClinical Epidemiology, 2013
- Neuronal Responses to Physiological StressFrontiers in Genetics, 2012
- Brain axonal and myelin evaluation in heart failureJournal of the Neurological Sciences, 2011
- Diastolic dysfunction and arrhythmias caused by overexpression of CaMKIIδC can be reversed by inhibition of late Na+ currentBasic Research in Cardiology, 2010
- Histone Methylation Regulates Memory FormationJournal of Neuroscience, 2010
- Cognitive Deficits in Chronic Heart FailureNursing Research, 2010
- Inhibitors of Class 1 Histone Deacetylases Reverse Contextual Memory Deficits in a Mouse Model of Alzheimer's DiseaseNeuropsychopharmacology, 2009
- Genome-wide Mapping of HATs and HDACs Reveals Distinct Functions in Active and Inactive GenesCell, 2009
- WGCNA: an R package for weighted correlation network analysisBMC Bioinformatics, 2008
- Combinatorial patterns of histone acetylations and methylations in the human genomeNature Genetics, 2008