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Prefrontal cortex miR-29b-3p plays a key role in the antidepressant-like effect of ketamine in rats
Yun-Qiang Wan,Jian-Guo Feng,Mao Li,Mao-Zhou Wang,Li Liu,Xueru Liu,Xiao-Xia Duan,Chun-Xiang Zhang,Xiao-Bin Wang 생화학분자생물학회 2018 Experimental and molecular medicine Vol.50 No.-
Ketamine has a rapid, obvious, and persistent antidepressant effect, but its underlying molecular mechanisms remain unknown. Recently, microRNAs (miRNAs) have emerged as important modulators of ketamine’s antidepressant effect. We investigated the alteration in miR-29b-3p in the brain of rats subjected to ketamine administration and chronic unpredictable mild stress (CUMS), and a sucrose preference test and forced swimming test were used to evaluate the rats’ depressive-like state. We used recombination adeno-associated virus (rAAV) or lentivirus-expressing miR-29b-3p to observe the change in metabotropic glutamate receptor 4 (GRM4). Cell culture and electrophysiological recordings were used to evaluate the function of miR-29b-3p. Ketamine dramatically increased miR-29b-3p expression in the prefrontal cortex of the normal rats. The dual luciferase reporter test confirmed that GRM4 was the target of miR-29b- 3p. The miR-29b-3p levels were downregulated, while the GRM4 levels were upregulated in the prefrontal cortex of the depressive-like rats. The ketamine treatment increased miR-29b-3p expression and decreased GRM4 expression in the prefrontal cortex of the depressive-like rats and primary neurons. By overexpressing and silencing miR-29b-3p, we further validated that miR-29b-3p could negatively regulate GRM4. The silencing of miR-29b-3p suppressed the Ca2+ influx in the prefrontal cortex neurons. The miR-29b-3p overexpression contributed to cell survival, cytodendrite growth, increases in extracellular glutamate concentration, and cell apoptosis inhibition. The overexpression of miR- 29b-3p by rAAV resulted in a noticeable relief of the depressive behaviors of the CUMS rats and a lower expression of GRM4. The miR-29b-3p/GRM4 pathway acts as a critical mediator of ketamine’s antidepressant effect in depressive-like rats and could be considered a potential therapeutic target for treating major depression disorder.
Yang, Yun,Peng, Wei,Tang, Tian,Xia, Lin,Wang, Xiao-Dong,Duan, Bao-Feng,Shu, Ye Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.13
Objective: In this study, tumor-stage predictive abilities of miR21, miR155, miR29a and miR92a were evaluated in rectal cancer (RC). Methods: Expression of miR21, miR155, miR29a and miR92a was detected and quantitated in tumor tissue and in adjacent normal tissue from 40 patients by TaqMan MicroRNA assay. Results: Significant overexpression of miR21, miR155, miR29a and miR92a was observed in RC tissues. While high expression of miR21, miR155 and miR29a in N1-2 and C-D stages presented a potential correlation with N and Duke stages, partial correlation analysis suggested that only miR155 rather than miR21 and miR29a played a greater influencing role. Receiver operating characteristics (ROC) curve analysis showed that miR155 could discriminate N0 from N1-2 with 85.0% sensitivity and 85.0% specificity, N2 from N0-1 with 90.0% sensitivity and 96.7% specificity, and C-D stage from A-B stage with 81.0% sensitivity and 84.2% specificity. Conclusions: Increase in expression of miR155 might represent a novel predictor for RC N and Dukes staging.
Sheng-hai Zhang,Ying-zi Wang,Fan-yun Meng,You-lin Li,Cai-xia Li,Fei-peng Duan,Qing Wang,Xiu-ting Zhang,Chun-ni Zhang 대한약학회 2015 Archives of Pharmacal Research Vol.38 No.5
Flavonoid glycosides are metabolized byintestinal bacteria, giving rise to a wide range of phenolicacids that may exert systemic effects in the body. Themicrobial metabolism of flavonoids extracted from theleaves of Diospyros kaki (FLDK) by intestinal bacteria wasinvestigated in vitro. High-performance liquid chromatography/linear trap quadrupole orbitrap mass spectrometrywas performed to analyze the metabolites of flavonoidsin vivo using Xcalibur2.1 software. The results showed thatthe levels of flavonoid glycosides and flavonoid aglyconesdecreased rapidly in the process of microbial metabolismby intestinal bacteria in vitro, and the metabolic rate maybe related to the concentration of intestinal bacteria in theculture solution. In vivo metabolites of FLDK weredetected in rat plasma and urine after oral administration ofFLDK. Eight flavonoids were identified in the urine, andthree were identified in the plasma; however, flavonoidaglycones were not found in the plasma.