Electroconvulsive Stimulation in Rats Induces Alterations in the Hippocampal miRNome: Translational Implications for Depression.

Thumbnail Image

Files

s12035-022-03131-8 (1).pdf (1.07 MB)

Authors

Ryan, Karen M
Smyth, Paul
Blackshields, Gordon
Kranaster, Laura
Sartorius, Alexander
Sheils, Orla
McLoughlin, Declan M

Issue Date

2022-11-22

Type

Journal Article

Language

en

Keywords

Depression , Electroconvulsive stimulation , Electroconvulsive therapy , Next-generation sequencing , microRNA

Research Projects

Organizational Units

Journal Issue

Alternative Title

Abstract

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.

Description

Citation

Ryan, K. M., Smyth, P., Blackshields, G., Kranaster, L., Sartorius, A., Sheils, O., & McLoughlin, D. M. (2023). Electroconvulsive Stimulation in Rats Induces Alterations in the Hippocampal miRNome: Translational Implications for Depression. Molecular neurobiology, 60(3), 1150–1163. https://doi.org/10.1007/s12035-022-03131-8

Publisher

License

© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.

Journal

Molecular neurobiology

Volume

60

Issue

3

URI

https://repository.stpatricks.ie/handle/123456789/39

PubMed ID

36414911

DOI

10.1007/s12035-022-03131-8
10.1016/S0140-6736(03)12705-5
10.1192/bjp.2021.37
10.1016/j.pnpbp.2011.12.012
10.1017/S1461145714000200
10.1016/j.bbrc.2004.12.050
10.1523/JNEUROSCI.15-11-07539.1995
10.1111/j.1460-9568.2006.04958.x
10.1002/syn.20538
10.1002/hipo.22670
10.1055/s-0029-1224162
10.1002/hipo.22171
10.1016/j.neulet.2013.05.035
10.1017/S1461145713000448
10.1111/acps.12821
10.1038/tp.2016.131
10.3390/cells8111465
10.1111/acps.12191
10.3389/fgene.2012.00082
10.1016/j.pneurobio.2019.101732
10.2147/Ndt.S237116
10.1590/1414-431X20187212
10.1371/journal.pone.0063648
10.2147/Ndt.S116287
10.1038/npp.2016.175
10.1016/j.jpsychires.2015.07.023
10.1038/nm.3582
10.1016/j.neulet.2021.136184
10.3390/cells8070647
10.3390/biomedicines9101428
10.1016/j.euroneuro.2012.06.013
10.1016/j.psychres.2018.09.025
10.1093/ijnp/pyx034
10.1038/s41380-021-01255-2
10.1186/s12911-019-0964-z
10.2147/NDT.S241136
10.1042/BSR20190186
10.26355/eurrev_202002_20197
10.1016/j.jad.2020.05.017
10.1038/s41398-021-01588-0
10.3390/ijms19030671
10.1136/jnnp.23.1.56
10.1176/appi.ajp.2015.15030372
10.1016/j.bbi.2019.10.005
10.1097/YCT.0000000000000667
10.1016/j.psyneuen.2018.12.234
10.1006/meth.2001.1262
10.3389/fendo.2018.00402
10.2217/pgs.12.93
10.1503/jpn.130169
10.1186/s13229-017-0149-5
10.1007/s12035-019-1524-3
10.1016/j.biopsych.2021.05.008
10.1016/bs.irn.2015.07.003
10.1080/21655979.2021.2009964
10.3390/nu13082885
10.1186/s12974-021-02299-5
10.1016/j.brs.2021.05.014
10.1038/s41380-021-01380-y
10.1109/IEMBS.2010.5626553
10.1002/hipo.20646
10.1016/j.jpsychires.2016.07.012
10.1016/j.pnpbp.2015.05.007
10.1016/j.jocn.2014.08.018
10.1016/j.jad.2017.11.090
10.1016/j.jpsychires.2015.01.006
10.1016/j.schres.2010.07.002
10.1016/j.bbi.2012.12.018
10.1186/s12935-021-02149-7
10.1007/s11033-022-07188-5
10.3389/fnins.2021.687973
10.3389/fnmol.2021.631553
10.1038/s41386-020-00861-y
10.1038/s41380-020-00953-7
10.1093/brain/awx366
10.1002/ajmg.b.32292
10.1073/pnas.1113793109
10.1042/BJ20100024
10.1371/journal.pone.0019077
10.1093/nar/gks151
10.1101/lm.039578.115
10.1073/pnas.1015691107
10.1007/s10571-019-00684-6
10.1016/j.psychres.2022.114390
10.3389/fphar.2017.00770
10.1016/j.brainres.2016.02.045
10.15252/embj.2018100481
10.14670/HH-18-266
10.1111/acel.12444
10.1177/09603271211009970
10.3390/cancers10060181
10.1016/j.neuropharm.2014.10.011
10.1007/s00406-014-0543-3
10.1111/acps.12951

ISSN

1559-1182

EISSN

Collections

Articles