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Epigenetic gene-expression links heart failure to memory impairment

Rezaul Islam, Dawid Lbik, Sadman Sakib, Raoul Maximilian Hofmann, Tea Berulava, Martí Jiménez Mausbach, Julia Cha, Elerdashvili Vakhtang, Christian Schiffmann, Anke Zieseniss, Dörthe Magdalena Katschinski, Farahnaz Sananbenesi, Karl Toischer, Andre Fischer
doi: https://doi.org/10.1101/2020.01.22.915637
Rezaul Islam
1Department for Systems Medicine and Epigenetics, German Center for Neurodegenerative Diseases (DZNE), Von Siebold Str. 3a, 37075, Göttingen, Germany
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Dawid Lbik
2Clinic of Cardiology and Pneumology, Georg-August-University, Göttingen, Germany
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Sadman Sakib
1Department for Systems Medicine and Epigenetics, German Center for Neurodegenerative Diseases (DZNE), Von Siebold Str. 3a, 37075, Göttingen, Germany
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Raoul Maximilian Hofmann
2Clinic of Cardiology and Pneumology, Georg-August-University, Göttingen, Germany
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Tea Berulava
1Department for Systems Medicine and Epigenetics, German Center for Neurodegenerative Diseases (DZNE), Von Siebold Str. 3a, 37075, Göttingen, Germany
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Martí Jiménez Mausbach
1Department for Systems Medicine and Epigenetics, German Center for Neurodegenerative Diseases (DZNE), Von Siebold Str. 3a, 37075, Göttingen, Germany
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Julia Cha
1Department for Systems Medicine and Epigenetics, German Center for Neurodegenerative Diseases (DZNE), Von Siebold Str. 3a, 37075, Göttingen, Germany
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Elerdashvili Vakhtang
1Department for Systems Medicine and Epigenetics, German Center for Neurodegenerative Diseases (DZNE), Von Siebold Str. 3a, 37075, Göttingen, Germany
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Christian Schiffmann
1Department for Systems Medicine and Epigenetics, German Center for Neurodegenerative Diseases (DZNE), Von Siebold Str. 3a, 37075, Göttingen, Germany
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Anke Zieseniss
3German Center for Cardiovascular Research (DZHK), partner site Göttingen, Germany
4Institute for Cardiovascular Physiology, University Medical Center, Georg-August University Göttingen, Germany
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Dörthe Magdalena Katschinski
3German Center for Cardiovascular Research (DZHK), partner site Göttingen, Germany
4Institute for Cardiovascular Physiology, University Medical Center, Georg-August University Göttingen, Germany
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Farahnaz Sananbenesi
5Genome Dynamics, German Center for Neurodegenerative Diseases (DZNE), Von Siebold Str. 3a, 37075, Göttingen, Germany
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Karl Toischer
2Clinic of Cardiology and Pneumology, Georg-August-University, Göttingen, Germany
3German Center for Cardiovascular Research (DZHK), partner site Göttingen, Germany
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  • For correspondence: andre.fischer@dzne.de ktoischer@med.uni-goettingen.de
Andre Fischer
1Department for Systems Medicine and Epigenetics, German Center for Neurodegenerative Diseases (DZNE), Von Siebold Str. 3a, 37075, Göttingen, Germany
6Department of Psychiatry and Psychotherapy, University Medical Center Göttingen, Germany
7Cluster of Excellence “Multiscale Bioimaging: from Molecular Machines to Networks of Excitable Cells” (MBExC), University of Göttingen, Germany
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  • For correspondence: andre.fischer@dzne.de ktoischer@med.uni-goettingen.de
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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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Posted January 23, 2020.
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Epigenetic gene-expression links heart failure to memory impairment
Rezaul Islam, Dawid Lbik, Sadman Sakib, Raoul Maximilian Hofmann, Tea Berulava, Martí Jiménez Mausbach, Julia Cha, Elerdashvili Vakhtang, Christian Schiffmann, Anke Zieseniss, Dörthe Magdalena Katschinski, Farahnaz Sananbenesi, Karl Toischer, Andre Fischer
bioRxiv 2020.01.22.915637; doi: https://doi.org/10.1101/2020.01.22.915637
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Epigenetic gene-expression links heart failure to memory impairment
Rezaul Islam, Dawid Lbik, Sadman Sakib, Raoul Maximilian Hofmann, Tea Berulava, Martí Jiménez Mausbach, Julia Cha, Elerdashvili Vakhtang, Christian Schiffmann, Anke Zieseniss, Dörthe Magdalena Katschinski, Farahnaz Sananbenesi, Karl Toischer, Andre Fischer
bioRxiv 2020.01.22.915637; doi: https://doi.org/10.1101/2020.01.22.915637

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