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@ARTICLE{Gisa:279375,
author = {Gisa, Verena and Islam, Md Rezaul and Lbik, Dawid and
Hofmann, Raoul Maximilian and Pena, Tonatiuh and Krüger,
Dennis Manfred and Burkhardt, Susanne and Schütz, Anna-Lena
and Sananbenesi, Farahnaz and Toischer, Karl and Fischer,
Andre},
title = {{R}ole of {C}ompensatory mi{RNA} {N}etworks in {C}ognitive
{R}ecovery from {H}eart {F}ailure.},
journal = {Non-Coding RNA},
volume = {11},
number = {3},
issn = {2311-553X},
address = {Basel},
publisher = {MDPI},
reportid = {DZNE-2025-00752},
pages = {45},
year = {2025},
abstract = {Background: Heart failure (HF) is associated with an
increased risk of cognitive impairment and hippocampal
dysfunction, yet the underlying molecular mechanisms remain
poorly understood. This study aims to investigate the role
of microRNA (miRNA) networks in hippocampus-dependent memory
recovery in a mouse model of HF. Methods: CaMKIIδC
transgenic (TG) mice, a model for HF, were used to assess
hippocampal function at 3 and 6 months of age. Memory
performance was evaluated using hippocampus-dependent
behavioral tasks. Small RNA sequencing was performed to
analyze hippocampal miRNA expression profiles across both
time points. Bioinformatic analyses identified miRNAs that
potentially regulate genes previously implicated in
HF-induced cognitive impairment. Results: We have previously
shown that at 3 months of age, CaMKIIδC TG mice exhibited
significant memory deficits associated with dysregulated
hippocampal gene expression. In this study, we showed that
these impairments, memory impairment and hippocampal gene
expression, were no longer detectable at 6 months, despite
persistent cardiac dysfunction. However, small RNA
sequencing revealed a dynamic shift in hippocampal miRNA
expression, identifying 27 miRNAs as 'compensatory miRs'
that targeted $73\%$ of the transcripts dysregulated at 3
months but reinstated by 6 months. Notably, miR-181a-5p
emerged as a central regulatory hub, with its downregulation
coinciding with restored memory function. Conclusions: These
findings suggest that miRNA networks contribute to the
restoration of hippocampal function in HF despite continued
cardiac pathology and provide an important compensatory
mechanism towards memory impairment. A better understanding
of these compensatory miRNA mechanisms may provide novel
therapeutic targets for managing HF-related cognitive
dysfunction.},
keywords = {Alzheimer (Other) / MicroRNA (Other) / cognitive impairment
(Other) / heart failure (Other) / hippocampal function
(Other) / memory recovery (Other) / transcriptional
homeostasis (Other)},
cin = {AG Fischer / Bioinformatics Unit (Göttingen) / AG
Sananbenesi},
ddc = {570},
cid = {I:(DE-2719)1410002 / I:(DE-2719)1440016 /
I:(DE-2719)1410004},
pnm = {352 - Disease Mechanisms (POF4-352) / 899 - ohne Topic
(POF4-899)},
pid = {G:(DE-HGF)POF4-352 / G:(DE-HGF)POF4-899},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:40559623},
pmc = {pmc:PMC12196295},
doi = {10.3390/ncrna11030045},
url = {https://pub.dzne.de/record/279375},
}