Genistein Improves the Major Depression through Suppressing the Expression of miR-221/222 by Targeting Connexin 43
0
조회
0
다운로드
1
인용
0
참고문헌
키워드
초록
Objective Recent studies have indicated the possibility that genistein may improve depression via regulating the expression of miR- 221/222. This study is to explore whether genistein could improve depression by altering miR-221/222 levels and investigate the possible mechanisms involved in the improvement effect of genistein. Methods The animal model of depression was established through unpredictable chronic mild stress. Nest building test and splash test were adapted to evaluate the effects of genistein on depressive symptoms in mice. qRT-PCR and western blot analysis were used to detect the expression of miR-221/222 and connexin 43 (Cx43) in the prefrontal cortex of the mice. In vitro, U87-MG astrocytes were treated with genistein and the expression of miR-221/222 and Cx43 was measured. The dual-luciferase reporter assay was used to verify whether Cx43 was a direct target of miR-221/222. Results The behavioral tests showed that genistein could significantly reduce depression symptoms of mice, and this remission was not affected by gender. Genistein in vivo and in vitro could reduce increased levels of miR-221 and miR-222 in the prefrontal cortex of depressed mice, while upregulate Cx43 expression. Dual-luciferase reporter assay suggested Cx43 was directly regulated by miR-221/222 in astrocytes. Conclusion Genistein can play its antidepressant effect through down-regulating miR-221/222 by targeting Cx43.
Abstract
Objective Recent studies have indicated the possibility that genistein may improve depression via regulating the expression of miR- 221/222. This study is to explore whether genistein could improve depression by altering miR-221/222 levels and investigate the possible mechanisms involved in the improvement effect of genistein. Methods The animal model of depression was established through unpredictable chronic mild stress. Nest building test and splash test were adapted to evaluate the effects of genistein on depressive symptoms in mice. qRT-PCR and western blot analysis were used to detect the expression of miR-221/222 and connexin 43 (Cx43) in the prefrontal cortex of the mice. In vitro, U87-MG astrocytes were treated with genistein and the expression of miR-221/222 and Cx43 was measured. The dual-luciferase reporter assay was used to verify whether Cx43 was a direct target of miR-221/222. Results The behavioral tests showed that genistein could significantly reduce depression symptoms of mice, and this remission was not affected by gender. Genistein in vivo and in vitro could reduce increased levels of miR-221 and miR-222 in the prefrontal cortex of depressed mice, while upregulate Cx43 expression. Dual-luciferase reporter assay suggested Cx43 was directly regulated by miR-221/222 in astrocytes. Conclusion Genistein can play its antidepressant effect through down-regulating miR-221/222 by targeting Cx43.
참고문헌 (21)
- Alvarez-Saavedra M, "miRNA-132 orchestrates chromatin remodeling and translational control of the circadian clock", Hum Mol Genet, 20, pp.731~751 (2011)[DOI]
- Anacker C, "The glucocorticoid receptor: pivot of depression and of antidepressant treatment", Psychoneuroendocrinology, 36, pp.415~425 (2011)[DOI]
- Kageyama A, "Genistein regulated serotonergic activity in the hippocampus of ovariectomized rats under forced swimming stress", Biosci Biotechnol Biochem, 74, pp.2005~2010 (2010)[DOI]
- Marini H, "Efficacy of genistein aglycone on some cardiovascular risk factors and homocysteine levels: a follow-up study", Nutr Metab Cardiovasc Dis, 20, pp.332~340 (2010)[DOI]
- Atteritano M, "Genistein effects on quality of life and depression symptoms in osteopenic postmenopausal women: a 2-year randomized, doubleblind, controlled study", Osteoporos Int, 25, pp.1123~1129 (2014)[DOI]
- Baffa A, "Norepinephrine and serotonin transporter genes: impact on treatment response in depression", Neuropsychobiology, 62, pp.121~131 (2010)[DOI]
- Baudry A, "New views on antidepressant action", Curr Opin Neurobiol, 21, pp.858~865 (2011)[DOI]
- Baudry A, "miR-16 targets the serotonin transporter: a new facet for adaptive responses to antidepressants", Science, 329, pp.1537~1541 (2010)[DOI]
- Smalheiser NR, "Expression of microRNAs and other small RNAs in prefrontal cortex in schizophrenia, bipolar disorder and depressed subjects", PLoS One, 9, pp.e86469~ (2014)[DOI]
- Wan Y, "Identification of differential microRNAs in cerebrospinal fluid and serum of patients with major depressive disorder", PLoS One, 10, pp.e0121975~ (2015)[DOI]
- Zhou R, "Evidence for selective microRNAs and their effectors as common longterm targets for the actions of mood stabilizers", Neuropsychopharmacology, 34, pp.1395~1405 (2009)[DOI]
- Oved K, "Genome-wide expression profiling of human lymphoblastoid cell lines implicates integrin beta-3 in the mode of action of antidepressants", Transl Psychiatry, 3, pp.e313~ (2013)[DOI]
- Chen Y, "MicroRNAs 221", 222 and genistein-mediated regulation of ARHI tumor suppressor gene in prostate cancer, 2011, pp.4, 76~86
- Hao J, "miR-221", 222 is the regulator of Cx43 expression in human glioblastoma cells, 2012, pp.27, 1504~1510
- Miguel-Hidalgo JJ, "Reduced connexin 43 immunolabeling in the orbitofrontal cortex in alcohol dependence and depression", J Psychiatr Res, 55, pp.101~109 (2014)[DOI]
- Nollet M, "Models of depression: unpredictable chronic mild stress in mice", Curr Protoc Pharmacol (2013)
- Abelaira HM, "The role of mTOR in depression and antidepressant responses", Life Sci, 101, pp.10~14 (2014)[DOI]
- Busch Y, "Blood-based biomarkers predicting response to antidepressants", Neural Transm (Vienna) (2018)
- Briley M, "Present and future anxiolytics", IDrugs, 3, pp.695~699 (2000)
- Avery-Kiejda KA, "The expression of Dicer and Drosha in matched normal tissues, tumours and lymph node metastases in triple negative breast cancer", BMC Cancer, 14, pp.253~ (2014)[DOI]
- Smalheiser NR, "MicroRNA expression is down-regulated and reorganized in prefrontal cortex of depressed suicide subjects", PLoS One, 7, pp.e33201~ (2012)[DOI]