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Dopamine Receptor D2 and Associated microRNAs Are Involved in Stress Susceptibility and Resistance to Escitalopram Treatment.

作者信息

Zhang Yi, Wang Yuting, Wang Lei, Bai Mei, Zhang Xiuwu, Zhu Xiongzhao

机构信息

Medical Psychological Institute, Second Xiangya Hospital, Central South University,Changsha, PR China (Drs Y. Zhang, Y. Wang, L. Wang, Bai, and Zhu); Department of Radiation Oncology, University of Maryland, Baltimore, MD (Drs Y. Zhang and X. Zhang); National Technology Institute of Psychiatry, Central South University, Changsha, PR China (Drs Y. Wang and L. Wang); Key Laboratory of Psychiatry and Mental Health of Hunan Province, Central South University, Changsha, PR China (Drs Bai and Zhu).

出版信息

Int J Neuropsychopharmacol. 2015 Mar 3;18(8):pyv025. doi: 10.1093/ijnp/pyv025.

DOI:10.1093/ijnp/pyv025
PMID:25740916
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4571637/
Abstract

BACKGROUND: Early life stress has been demonstrated to increase the risk of developing depression in adulthood. However, the roles and associated molecular mechanisms of stresses in the onset and relapse of depression have yet to be fully elucidated. METHODS: Depression-like behaviors were induced in rats by maternal deprivation and chronic unpredictable stress. Depression- and anxiety-like behaviors of rats, dopamine receptor D2 level, and microRNAs expression in rats' brain tissues were measured. RESULTS: Chronic unpredictable stress alone induced depression-like behaviors in rats, but maternal deprivation enhanced the effect of chronic unpredictable stress. Escitalopram significantly decreased depression-like behaviors in chronic unpredictable stress rats but was less effective in maternal deprivation with chronic unpredictable stress rats. Maternal deprivation increased dopamine receptor D2 messenger RNA expression and decreased microRNA-9 expression in the striatum. Chronic unpredictable stress increased dopamine receptor D2 mRNA and protein levels and decreased microRNA-9 expression in the nucleus accumbens. Furthermore, maternal deprivation enhanced the effect of chronic unpredictable stress on dopamine receptor D2 gene and microRNA-9 expression. Chronic unpredictable stress increased the expression of microRNA-326 in the nucleus accumbens but decreased it in the striatum, whereas maternal deprivation elevated microRNA-326 expression in the striatum. Escitalopram normalized microRNA-326 expression but had no effect on the expression of microRNA-9, dopamine receptor D2 mRNA, and dopamine receptor D2 protein in both the nucleus accumbens and striatum. The in vitro study showed that only microRNA-9 directly targeted the 3' untranslated region of dopamine receptor D2 mRNA and inhibited dopamine receptor D2 protein expression. CONCLUSION: Early life stress enhanced the susceptibility to late life stress and resistance to escitalopram treatment through decreasing microRNA-9 expression and subsequently upregulating dopamine receptor D2 expression in the nucleus accumbens. microRNA-326 may be a novel target of escitalopram.

摘要
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6751/4571637/54c960cfe1ce/ijnppy_pyv025_f0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6751/4571637/6578d27da690/ijnppy_pyv025_f0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6751/4571637/0ec1bd5af340/ijnppy_pyv025_f0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6751/4571637/e6cd2b7dc264/ijnppy_pyv025_f0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6751/4571637/54c960cfe1ce/ijnppy_pyv025_f0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6751/4571637/6578d27da690/ijnppy_pyv025_f0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6751/4571637/0ec1bd5af340/ijnppy_pyv025_f0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6751/4571637/e6cd2b7dc264/ijnppy_pyv025_f0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6751/4571637/54c960cfe1ce/ijnppy_pyv025_f0004.jpg

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本文引用的文献

[1]
Maternal deprivation enhances behavioral vulnerability to stress associated with miR-504 expression in nucleus accumbens of rats.

PLoS One. 2013-7-26

[2]
Escitalopram for the management of major depressive disorder: a review of its efficacy, safety, and patient acceptability.

Patient Prefer Adherence. 2012

[3]
Abnormal hippocampal BDNF and miR-16 expression is associated with depression-like behaviors induced by stress during early life.

PLoS One. 2012-10-8

[4]
Normal midbrain dopaminergic neuron development and function in miR-133b mutant mice.

J Neurosci. 2012-8-8

[5]
Little things on which happiness depends: microRNAs as novel therapeutic targets for the treatment of anxiety and depression.

Mol Psychiatry. 2011-12-20

[6]
Early-life stress mediated modulation of adult neurogenesis and behavior.

Behav Brain Res. 2011-7-28

[7]
Classification of trauma and stressor-related disorders in DSM-5.

Depress Anxiety. 2011-6-16

[8]
Stress-induced depressive behaviors are correlated with Par-4 and DRD2 expression in rat striatum.

Behav Brain Res. 2011-5-8

[9]
Binge cocaine administration in adolescent rats affects amygdalar gene expression patterns and alters anxiety-related behavior in adulthood.

Biol Psychiatry. 2011-5-14

[10]
The mesoaccumbens dopamine in coping with stress.

Neurosci Biobehav Rev. 2011-5-4

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