MicroRNA-202-3p Targets Brain-Derived Neurotrophic Factor and Is Involved in Depression-Like Behaviors

Overview

Journal Neuropsychiatr Dis Treat

Publisher Dove Medical Press

Specialty Psychiatry

Date 2020 May 20

PMID 32425535

Citations 11

Authors

Cuiyu Xin

Jiejing Xia

Yulan Liu

Yongdong Zhang

Affiliations

Soon will be listed here.

Abstract

Background: Brain-derived neurotrophic factor (BDNF) and microRNA (miRNA) play crucial roles in the etiology of depression. However, the molecular mechanisms underlying this disease are not fully understood. The primary objective of this study was to investigate the relationship between miR-202-3p and BDNF in a chronic unpredictable mild stress (CUMS) model.

Methods: Depression model was established with chronic mild unpredictable mild stimulation (CUMS) combined with solitary feeding. The expression levels of miR-202-3p and BDNF in rat hippocampus were measured by qRT-PCR. The novelty inhibition feeding test (NSFT), sucrose preference test (SPT), and forced swimming test (FST) were used to evaluate the functions of miR-202-3p and BDNF. Target gene prediction and screening and luciferase reporter assay were used to verify the target of miR-202-3p. The expression levels of BNDF, CREB1 and p-CREB1 were detected by Western blot.

Results: Upregulation of miR-202-3p was associated with decreased expression of BDNF in the hippocampus of the CUMS model. Antidepressant was observed when LV-BDNF or LV-si-miR-202-3p was injected into the hippocampus. In addition, in the rat hippocampus and cultured nerve cells, the expression levels of BDNF and cyclic AMP response element binding protein 1 (CREB1), which is a target gene of BDNF, were reduced after LV-miR-202-3p injection. Overexpression of miR-202-3p aggravated depressive behavior and decreased the expression levels of BDNF. Luciferase reporter assay also confirmed that BDNF was a target of miR-202-3p.

Conclusion: Silencing miR-202-3p can reduce the damage to hippocampal nerve in CUMS rats; the mechanism may be related to the upregulation of BNDF expression. miR-202-3p may be an effective target for the treatment of depression.

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References

Tavakolizadeh J, Roshanaei K, Salmaninejad A, Yari R, Nahand J, Sarkarizi H . MicroRNAs and exosomes in depression: Potential diagnostic biomarkers. J Cell Biochem. 2017; 119(5):3783-3797. DOI: 10.1002/jcb.26599. View

Farahani M, Rubbi C, Liu L, Slupsky J, Kalakonda N . CLL Exosomes Modulate the Transcriptome and Behaviour of Recipient Stromal Cells and Are Selectively Enriched in miR-202-3p. PLoS One. 2015; 10(10):e0141429. PMC: 4625016. DOI: 10.1371/journal.pone.0141429. View

Bian B, Yu X, Wang G, Teng T . Role of miRNA-1 in regulating connexin 43 in ischemia-reperfusion heart injury: a rat model. Cardiovasc Pathol. 2017; 27:37-42. DOI: 10.1016/j.carpath.2016.12.006. View

Kim J, Lee D, Kim J, Choi S, Park W, Ha K . A miRNA-101-3p/Bim axis as a determinant of serum deprivation-induced endothelial cell apoptosis. Cell Death Dis. 2017; 8(5):e2808. PMC: 5520733. DOI: 10.1038/cddis.2017.219. View

. Depression During Pregnancy. J Midwifery Womens Health. 2017; 62(6):779-780. DOI: 10.1111/jmwh.12678. View

Sharma R, Schuhmacher M, Kumar V . Developing integrated PBPK/PD coupled mechanistic pathway model (miRNA-BDNF): An approach towards system toxicology. Toxicol Lett. 2017; 280:79-91. DOI: 10.1016/j.toxlet.2017.08.003. View

Hua F, Liu S, Zhu L, Wang Y, Liang X, Ma N . MiRNA-338-3p regulates cervical cancer cells proliferation by targeting MACC1 through MAPK signaling pathway. Eur Rev Med Pharmacol Sci. 2017; 21(23):5342-5352. DOI: 10.26355/eurrev_201712_13919. View

Goodyer I, Herbert J, Tamplin A, Altham P . Recent life events, cortisol, dehydroepiandrosterone and the onset of major depression in high-risk adolescents. Br J Psychiatry. 2000; 177:499-504. DOI: 10.1192/bjp.177.6.499. View

Hohjoh H, Fukushima T . Expression profile analysis of microRNA (miRNA) in mouse central nervous system using a new miRNA detection system that examines hybridization signals at every step of washing. Gene. 2007; 391(1-2):39-44. DOI: 10.1016/j.gene.2006.11.018. View

10.

Peckham-Gregory E, Thapa D, Martinson J, Duggal P, Penugonda S, Bream J . MicroRNA-related polymorphisms and non-Hodgkin lymphoma susceptibility in the Multicenter AIDS Cohort Study. Cancer Epidemiol. 2016; 45:47-57. PMC: 5127653. DOI: 10.1016/j.canep.2016.09.007. View

11.

Jaitner C, Reddy C, Abentung A, Whittle N, Rieder D, Delekate A . Satb2 determines miRNA expression and long-term memory in the adult central nervous system. Elife. 2016; 5. PMC: 5207769. DOI: 10.7554/eLife.17361. View

12.

Wu F, Li L, Wen Q, Yang J, Chen Z, Wu P . A functional variant in ST2 gene is associated with risk of hypertension via interfering MiR-202-3p. J Cell Mol Med. 2017; 21(7):1292-1299. PMC: 5487927. DOI: 10.1111/jcmm.13058. View

13.

Li Y, Xu M, Gao Z, Wang Y, Yue Z, Zhang Y . Alterations of serum levels of BDNF-related miRNAs in patients with depression. PLoS One. 2013; 8(5):e63648. PMC: 3660391. DOI: 10.1371/journal.pone.0063648. View

14.

Kynast K, Russe O, Moser C, Geisslinger G, Niederberger E . Modulation of central nervous system-specific microRNA-124a alters the inflammatory response in the formalin test in mice. Pain. 2013; 154(3):368-376. DOI: 10.1016/j.pain.2012.11.010. View

15.

Sanchez-Campillo M, Bini L, Comanducci M, Raggiaschi R, Marzocchi B, Pallini V . Identification of immunoreactive proteins of Chlamydia trachomatis by Western blot analysis of a two-dimensional electrophoresis map with patient sera. Electrophoresis. 1999; 20(11):2269-79. DOI: 10.1002/(SICI)1522-2683(19990801)20:11<2269::AID-ELPS2269>3.0.CO;2-D. View

16.

Aghaee-Bakhtiari S, Arefian E, Lau P . miRandb: a resource of online services for miRNA research. Brief Bioinform. 2017; 18(5):904. DOI: 10.1093/bib/bbx027. View

17.

Sanna M, Mello T, Masini E, Galeotti N . Activation of ERK/CREB pathway in noradrenergic neurons contributes to hypernociceptive phenotype in H4 receptor knockout mice after nerve injury. Neuropharmacology. 2017; 128:340-350. DOI: 10.1016/j.neuropharm.2017.10.025. View

18.

Liu W, Xue X, Xia J, Liu J, Qi Z . Swimming exercise reverses CUMS-induced changes in depression-like behaviors and hippocampal plasticity-related proteins. J Affect Disord. 2017; 227:126-135. DOI: 10.1016/j.jad.2017.10.019. View

19.

Chrivia J, Kwok R, Lamb N, Hagiwara M, Montminy M, Goodman R . Phosphorylated CREB binds specifically to the nuclear protein CBP. Nature. 1993; 365(6449):855-9. DOI: 10.1038/365855a0. View

20.

Smolderen K, Spertus J, Gosch K, Dreyer R, DOnofrio G, Lichtman J . Depression Treatment and Health Status Outcomes in Young Patients With Acute Myocardial Infarction: Insights From the VIRGO Study (Variation in Recovery: Role of Gender on Outcomes of Young AMI Patients). Circulation. 2017; 135(18):1762-1764. PMC: 5755692. DOI: 10.1161/CIRCULATIONAHA.116.027042. View