Electroconvulsive stimulation in rats induces alterations in the hippocampal miRNome: translational implications for depression

MicroRNAs (miRNAs) may contribute to the development of depression and its treatment. Here, we used the hypothesis-neutral approach of next-generation sequencing (NGS) to gain comprehensive understanding of the effects of a course of electroconvulsive stimulation (ECS), the animal model equivalent o...

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Main Authors: Ryan, Karen M. (Author) , Smyth, Paul (Author) , Blackshields, Gordon (Author) , Kranaster, Laura (Author) , Sartorius, Alexander (Author) , Sheils, Orla (Author) , McLoughlin, Declan M. (Author)
Format: Article (Journal)
Language:English
Published: March 2023
In: Molecular neurobiology
Year: 2023, Volume: 60, Issue: 3, Pages: 1150-1163
ISSN:1559-1182
DOI:10.1007/s12035-022-03131-8
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1007/s12035-022-03131-8
Verlag, lizenzpflichtig, Volltext: https://link.springer.com/article/10.1007/s12035-022-03131-8
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Author Notes:Karen M. Ryan, Paul Smyth, Gordon Blackshields, Laura Kranaster, Alexander Sartorius, Orla Sheils, Declan M. McLoughlin
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Summary:MicroRNAs (miRNAs) may contribute to the development of depression and its treatment. Here, we used the hypothesis-neutral approach of next-generation sequencing (NGS) to gain comprehensive understanding of the effects of a course of electroconvulsive stimulation (ECS), the animal model equivalent of electroconvulsive therapy (ECT), on rat hippocampal miRNAs. Significant differential expression (p < 0.001) of six hippocampal miRNAs was noted following NGS, after correcting for multiple comparisons. Three of these miRNAs were upregulated (miR-132, miR-212, miR-331) and three downregulated (miR-204, miR-483, miR-301a). qRT-PCR confirmed significant changes in four of the six miRNAs (miR-132, miR-212, miR-204, miR-483). miR-483 was also significantly reduced in frontal cortex, though no other significant alterations were noted in frontal cortex, cerebellum, or whole blood. Assessing the translatability of the results, miR-132 and miR-483 were significantly reduced in whole blood samples from medicated patients with depression (n = 50) compared to healthy controls (n = 45), though ECT had no impact on miRNA levels. Notably, pre-ECT miR-204 levels moderately positively correlated with depression severity at baseline and moderately negatively correlated with mood score reduction post-ECT. miRNAs were also examined in cerebrospinal fluid and serum from a separate cohort of patients (n = 8) treated with ECT; no significant changes were noted post-treatment. However, there was a large positive correlation between changes in miR-212 and mood score post-ECT in serum. Though replication studies using larger sample sizes are required, alterations in miRNA expression may be informative about the mechanism of action of ECS/ECT and in turn might give insight into the neurobiology of depression.
Item Description:Online veröffentlicht: 22. November 2022
Gesehen am 23.07.2024
Physical Description:Online Resource
ISSN:1559-1182
DOI:10.1007/s12035-022-03131-8