Psychiatry Investig.  2018 Oct;15(10):919-925. 10.30773/pi.2018.06.29.

Genistein Improves the Major Depression through Suppressing the Expression of miR-221/222 by Targeting Connexin 43

• Shen F
• Huang WL
• Xing BP
• Fang X
• Feng M
• Jiang CM

• KMID: 2425502
• DOI: http://doi.org/10.30773/pi.2018.06.29

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.

Keyword

Genistein; Major depression; miR-221/222; Cx43

MeSH Terms

Animals
Astrocytes
Behavior Rating Scale
Blotting, Western
Connexin 43*
Depression*
Genistein*
In Vitro Techniques
Mice
Models, Animal
Prefrontal Cortex
Connexin 43
Genistein