The Role of MicroRNAs in Depression

Overview

Journal Front Pharmacol

Date 2023 Apr 17

PMID 37063278

Authors

Ruidong Ding

Dingyuan Su

Qian Zhao

Yu Wang

Jia-Yi Wang

Shuangyu Lv

Xinying Ji

Affiliations

Soon will be listed here.

Abstract

Major depressive disorder (MDD) is a psychiatric disorder with increasing prevalence worldwide. It is a leading cause of disability and suicide, severely affecting physical and mental health. However, the study of depression remains at an exploratory stage in terms of diagnostics and treatment due to the complexity of its pathogenesis. MicroRNAs are endogenous short-stranded non-coding RNAs capable of binding to the 3'untranslated region of mRNAs. Because of their ability to repress translation process of genes and are found at high levels in brain tissues, investigation of their role in depression has gradually increased recently. This article summarizes recent research progress on the relationship between microRNAs and depression. The microRNAs play a regulatory role in the pathophysiology of depression, involving dysregulation of monoamines, abnormalities in neuroplasticity and neurogenesis, hyperactivity of the HPA axis, and dysregulation of inflammatory responses. These microRNAs might provide new clue for the diagnosis and treatment of MDD, and the development of antidepressant drugs.

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References

Petra A, Panagiotidou S, Hatziagelaki E, Stewart J, Conti P, Theoharides T . Gut-Microbiota-Brain Axis and Its Effect on Neuropsychiatric Disorders With Suspected Immune Dysregulation. Clin Ther. 2015; 37(5):984-95. PMC: 4458706. DOI: 10.1016/j.clinthera.2015.04.002. View

Kiecolt-Glaser J, Derry H, Fagundes C . Inflammation: depression fans the flames and feasts on the heat. Am J Psychiatry. 2015; 172(11):1075-91. PMC: 6511978. DOI: 10.1176/appi.ajp.2015.15020152. View

Segal D, Kuczenski R, Mandell A . Theoretical implications of drug-induced adaptive regulation for a biogenic amine hypothesis of affective disorder. Biol Psychiatry. 1974; 9(2):147-59. View

Huang P, Wei S, Luo M, Tang Z, Lin Q, Wang X . MiR-139-5p has an antidepressant-like effect by targeting phosphodiesterase 4D to activate the cAMP/PKA/CREB signaling pathway. Ann Transl Med. 2021; 9(20):1594. PMC: 8576692. DOI: 10.21037/atm-21-5149. View

Malhi G, Mann J . Depression. Lancet. 2018; 392(10161):2299-2312. DOI: 10.1016/S0140-6736(18)31948-2. View

Lopez J, Fiori L, Gross J, Labonte B, Yerko V, Mechawar N . Regulatory role of miRNAs in polyamine gene expression in the prefrontal cortex of depressed suicide completers. Int J Neuropsychopharmacol. 2013; 17(1):23-32. DOI: 10.1017/S1461145713000941. View

Uchida S, Nishida A, Hara K, Kamemoto T, Suetsugi M, Fujimoto M . Characterization of the vulnerability to repeated stress in Fischer 344 rats: possible involvement of microRNA-mediated down-regulation of the glucocorticoid receptor. Eur J Neurosci. 2008; 27(9):2250-61. DOI: 10.1111/j.1460-9568.2008.06218.x. View

Al-Rawaf H, Alghadir A, Gabr S . Circulating microRNAs and Molecular Oxidative Stress in Older Adults with Neuroprogression Disorders. Dis Markers. 2021; 2021:4409212. PMC: 8556086. DOI: 10.1155/2021/4409212. View

Yoshii A, Constantine-Paton M . Postsynaptic BDNF-TrkB signaling in synapse maturation, plasticity, and disease. Dev Neurobiol. 2010; 70(5):304-22. PMC: 2923204. DOI: 10.1002/dneu.20765. View

10.

Numakawa T, Adachi N, Richards M, Chiba S, Kunugi H . The influence of glucocorticoids on neuronal survival and synaptic function. Biomol Concepts. 2014; 3(6):495-504. DOI: 10.1515/bmc-2012-0012. View

11.

Su B, Cheng S, Wang L, Wang B . MicroRNA-139-5p acts as a suppressor gene for depression by targeting nuclear receptor subfamily 3, group C, member 1. Bioengineered. 2022; 13(5):11856-11866. PMC: 9276025. DOI: 10.1080/21655979.2022.2059937. View

12.

Herzog P, Dvorakova M, Zvolsky P . [T and B lymphocytes in psychotic patients (author's transl)]. Cesk Psychiatr. 1979; 75(3):153-9. View

13.

Smalheiser N, Lugli G, Rizavi H, Torvik V, Turecki G, Dwivedi Y . MicroRNA expression is down-regulated and reorganized in prefrontal cortex of depressed suicide subjects. PLoS One. 2012; 7(3):e33201. PMC: 3302855. DOI: 10.1371/journal.pone.0033201. View

14.

Zhao L, Yang X, Cui L, Wei J, Ni P, Li M . Increased expression of a novel miRNA in peripheral blood is negatively correlated with hippocampal volume in patients with major depressive disorder. J Affect Disord. 2018; 245:205-212. DOI: 10.1016/j.jad.2018.10.363. View

15.

Budziszewska B . Effect of antidepressant drugs on the hypothalamic-pituitary-adrenal axis activity and glucocorticoid receptor function. Pol J Pharmacol. 2003; 54(4):343-9. View

16.

Feng J, Wang M, Li M, Yang J, Jia J, Liu L . Serum miR-221-3p as a new potential biomarker for depressed mood in perioperative patients. Brain Res. 2019; 1720:146296. DOI: 10.1016/j.brainres.2019.06.015. View

17.

Friedman R, Farh K, Burge C, Bartel D . Most mammalian mRNAs are conserved targets of microRNAs. Genome Res. 2008; 19(1):92-105. PMC: 2612969. DOI: 10.1101/gr.082701.108. View

18.

Harrison N, Brydon L, Walker C, Gray M, Steptoe A, Dolan R . Neural origins of human sickness in interoceptive responses to inflammation. Biol Psychiatry. 2009; 66(5):415-22. PMC: 2885492. DOI: 10.1016/j.biopsych.2009.03.007. View

19.

Gibney S, Drexhage H . Evidence for a dysregulated immune system in the etiology of psychiatric disorders. J Neuroimmune Pharmacol. 2013; 8(4):900-20. DOI: 10.1007/s11481-013-9462-8. View

20.

Liu W, Zhang F, Zheng Y, He S, Zhang T, Guo Q . The role of circulating blood microRNA-374 and microRNA-10 levels in the pathogenesis and therapeutic mechanisms of major depressive disorder. Neurosci Lett. 2021; 763:136184. DOI: 10.1016/j.neulet.2021.136184. View