TY  - JOUR
AU  - Islam, Rezaul
AU  - Lbik, Dawid
AU  - Sakib, M Sadman
AU  - Maximilian Hofmann, Raoul
AU  - Berulava, Tea
AU  - Jiménez Mausbach, Martí
AU  - Cha, Julia
AU  - Goldberg, Maria
AU  - Elerdashvili, Vakhtang
AU  - Schiffmann, Christian
AU  - Zieseniss, Anke
AU  - Katschinski, Dörthe Magdalena
AU  - Sananbenesi, Farahnaz
AU  - Toischer, Karl
AU  - Fischer, Andre
TI  - Epigenetic gene expression links heart failure to memory impairment.
JO  - EMBO molecular medicine
VL  - 13
IS  - 3
SN  - 1757-4684
CY  - Heidelberg
PB  - EMBO Press
M1  - DZNE-2021-01172
SP  - e11900
PY  - 2021
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.
KW  - Animals
KW  - Cognition
KW  - Epigenesis, Genetic
KW  - Gene Expression
KW  - Heart Failure: genetics
KW  - Humans
KW  - Memory Disorders
KW  - Mice
KW  - cognition (Other)
KW  - epigenetics (Other)
KW  - heart failure (Other)
KW  - histone (Other)
KW  - memory impairment (Other)
LB  - PUB:(DE-HGF)16
C6  - pmid:33471428
C2  - pmc:PMC7933944
DO  - DOI:10.15252/emmm.201911900
UR  - https://pub.dzne.de/record/157715
ER  -