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000279375 1001_ $$0P:(DE-2719)9001957$$aGisa, Verena$$b0$$eFirst author
000279375 245__ $$aRole of Compensatory miRNA Networks in Cognitive Recovery from Heart Failure.
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000279375 520__ $$aBackground: 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.
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000279375 650_7 $$2Other$$aAlzheimer
000279375 650_7 $$2Other$$aMicroRNA
000279375 650_7 $$2Other$$acognitive impairment
000279375 650_7 $$2Other$$aheart failure
000279375 650_7 $$2Other$$ahippocampal function
000279375 650_7 $$2Other$$amemory recovery
000279375 650_7 $$2Other$$atranscriptional homeostasis
000279375 7001_ $$0P:(DE-2719)2811643$$aIslam, Md Rezaul$$b1$$udzne
000279375 7001_ $$00000-0003-2950-9487$$aLbik, Dawid$$b2
000279375 7001_ $$aHofmann, Raoul Maximilian$$b3
000279375 7001_ $$0P:(DE-2719)2811063$$aPena, Tonatiuh$$b4$$udzne
000279375 7001_ $$0P:(DE-2719)2812548$$aKrüger, Dennis Manfred$$b5$$udzne
000279375 7001_ $$0P:(DE-2719)2810773$$aBurkhardt, Susanne$$b6$$udzne
000279375 7001_ $$0P:(DE-2719)2810585$$aSchütz, Anna-Lena$$b7$$udzne
000279375 7001_ $$0P:(DE-2719)2811099$$aSananbenesi, Farahnaz$$b8$$udzne
000279375 7001_ $$aToischer, Karl$$b9
000279375 7001_ $$0P:(DE-2719)2000047$$aFischer, Andre$$b10$$eLast author
000279375 773__ $$0PERI:(DE-600)2813993-8$$a10.3390/ncrna11030045$$gVol. 11, no. 3, p. 45 -$$n3$$p45$$tNon-Coding RNA$$v11$$x2311-553X$$y2025
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