RT Journal Article
SR Electronic
T1 Epigenetic gene-expression links heart failure to memory impairment
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2020.01.22.915637
DO 10.1101/2020.01.22.915637
A1 Rezaul Islam
A1 Dawid Lbik
A1 Sadman Sakib
A1 Raoul Maximilian Hofmann
A1 Tea Berulava
A1 Martí Jiménez Mausbach
A1 Julia Cha
A1 Elerdashvili Vakhtang
A1 Christian Schiffmann
A1 Anke Zieseniss
A1 Dörthe Magdalena Katschinski
A1 Farahnaz Sananbenesi
A1 Karl Toischer
A1 Andre Fischer
YR 2020
UL http://biorxiv.org/content/early/2020/01/23/2020.01.22.915637.abstract
AB 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.