Role of Compensatory miRNA Networks in Cognitive Recovery from Heart Failure
<b>Background:</b> 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...
Saved in:
| Main Authors: | , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2025-06-01
|
| Series: | Non-Coding RNA |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2311-553X/11/3/45 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849432522468884480 |
|---|---|
| author | Verena Gisa Md Rezaul Islam Dawid Lbik Raoul Maximilian Hofmann Tonatiuh Pena Dennis Manfred Krüger Susanne Burkhardt Anna-Lena Schütz Farahnaz Sananbenesi Karl Toischer Andre Fischer |
| author_facet | Verena Gisa Md Rezaul Islam Dawid Lbik Raoul Maximilian Hofmann Tonatiuh Pena Dennis Manfred Krüger Susanne Burkhardt Anna-Lena Schütz Farahnaz Sananbenesi Karl Toischer Andre Fischer |
| author_sort | Verena Gisa |
| collection | DOAJ |
| description | <b>Background:</b> 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. <b>Methods:</b> 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. <b>Results:</b> 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. <b>Conclusions:</b> 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. |
| format | Article |
| id | doaj-art-99e24fec026742be99cd1aee74506b5d |
| institution | Kabale University |
| issn | 2311-553X |
| language | English |
| publishDate | 2025-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Non-Coding RNA |
| spelling | doaj-art-99e24fec026742be99cd1aee74506b5d2025-08-20T03:27:21ZengMDPI AGNon-Coding RNA2311-553X2025-06-011134510.3390/ncrna11030045Role of Compensatory miRNA Networks in Cognitive Recovery from Heart FailureVerena Gisa0Md Rezaul Islam1Dawid Lbik2Raoul Maximilian Hofmann3Tonatiuh Pena4Dennis Manfred Krüger5Susanne Burkhardt6Anna-Lena Schütz7Farahnaz Sananbenesi8Karl Toischer9Andre Fischer10Department for Epigenetics and Systems Medicine in Neurodegenerative Diseases, German Center for Neurodegenerative Diseases, Von Siebold Street 3A, 37075 Goettingen, GermanyDepartment for Epigenetics and Systems Medicine in Neurodegenerative Diseases, German Center for Neurodegenerative Diseases, Von Siebold Street 3A, 37075 Goettingen, GermanyClinic of Cardiology and Pneumology, Georg-August-University, Robert-Koch Street 38, 37075 Goettingen, GermanyClinic of Cardiology and Pneumology, Georg-August-University, Robert-Koch Street 38, 37075 Goettingen, GermanyDepartment for Epigenetics and Systems Medicine in Neurodegenerative Diseases, German Center for Neurodegenerative Diseases, Von Siebold Street 3A, 37075 Goettingen, GermanyDepartment for Epigenetics and Systems Medicine in Neurodegenerative Diseases, German Center for Neurodegenerative Diseases, Von Siebold Street 3A, 37075 Goettingen, GermanyDepartment for Epigenetics and Systems Medicine in Neurodegenerative Diseases, German Center for Neurodegenerative Diseases, Von Siebold Street 3A, 37075 Goettingen, GermanyResearch Group for Genome Dynamics in Brain Diseases, German Center for Neurodegenerative Diseases, Von Siebold Street 3A, 37075 Göttingen, GermanyResearch Group for Genome Dynamics in Brain Diseases, German Center for Neurodegenerative Diseases, Von Siebold Street 3A, 37075 Göttingen, GermanyClinic of Cardiology and Pneumology, Georg-August-University, Robert-Koch Street 38, 37075 Goettingen, GermanyDepartment for Epigenetics and Systems Medicine in Neurodegenerative Diseases, German Center for Neurodegenerative Diseases, Von Siebold Street 3A, 37075 Goettingen, Germany<b>Background:</b> 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. <b>Methods:</b> 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. <b>Results:</b> 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. <b>Conclusions:</b> 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.https://www.mdpi.com/2311-553X/11/3/45heart failurecognitive impairmenthippocampal functionMicroRNAtranscriptional homeostasismemory recovery |
| spellingShingle | Verena Gisa Md Rezaul Islam Dawid Lbik Raoul Maximilian Hofmann Tonatiuh Pena Dennis Manfred Krüger Susanne Burkhardt Anna-Lena Schütz Farahnaz Sananbenesi Karl Toischer Andre Fischer Role of Compensatory miRNA Networks in Cognitive Recovery from Heart Failure Non-Coding RNA heart failure cognitive impairment hippocampal function MicroRNA transcriptional homeostasis memory recovery |
| title | Role of Compensatory miRNA Networks in Cognitive Recovery from Heart Failure |
| title_full | Role of Compensatory miRNA Networks in Cognitive Recovery from Heart Failure |
| title_fullStr | Role of Compensatory miRNA Networks in Cognitive Recovery from Heart Failure |
| title_full_unstemmed | Role of Compensatory miRNA Networks in Cognitive Recovery from Heart Failure |
| title_short | Role of Compensatory miRNA Networks in Cognitive Recovery from Heart Failure |
| title_sort | role of compensatory mirna networks in cognitive recovery from heart failure |
| topic | heart failure cognitive impairment hippocampal function MicroRNA transcriptional homeostasis memory recovery |
| url | https://www.mdpi.com/2311-553X/11/3/45 |
| work_keys_str_mv | AT verenagisa roleofcompensatorymirnanetworksincognitiverecoveryfromheartfailure AT mdrezaulislam roleofcompensatorymirnanetworksincognitiverecoveryfromheartfailure AT dawidlbik roleofcompensatorymirnanetworksincognitiverecoveryfromheartfailure AT raoulmaximilianhofmann roleofcompensatorymirnanetworksincognitiverecoveryfromheartfailure AT tonatiuhpena roleofcompensatorymirnanetworksincognitiverecoveryfromheartfailure AT dennismanfredkruger roleofcompensatorymirnanetworksincognitiverecoveryfromheartfailure AT susanneburkhardt roleofcompensatorymirnanetworksincognitiverecoveryfromheartfailure AT annalenaschutz roleofcompensatorymirnanetworksincognitiverecoveryfromheartfailure AT farahnazsananbenesi roleofcompensatorymirnanetworksincognitiverecoveryfromheartfailure AT karltoischer roleofcompensatorymirnanetworksincognitiverecoveryfromheartfailure AT andrefischer roleofcompensatorymirnanetworksincognitiverecoveryfromheartfailure |