MicroRNA-135b-5p Downregulation Causes Antidepressant Effects by Regulating SIRT1 Expression.

Depression is a serious and potentially life-threatening mental illness. Recently, the role of sirtuin 1 (SIRT1) in chronic unpredictable mild stress (CUMS) management has been examined. The present study explored and clarified whether microRNA (miR)-135b-5p could play a role in depression by regulating the expression of SIRT1. SIRT1 was identified as the target gene of miR-135b-5p using TargetScan and the dual luciferase reporter assay. In addition, the expression levels of SIRT1 were significantly reduced in mouse peripheral blood and hippocampal tissue samples, while the expression of miR-135b-5p exhibited the opposite effects. Subsequently, the effects of miR-135b-5p inhibition were investigated in mice with depression. The results indicated that the miR-135b-5p inhibitor significantly increased the weight loss induced by CUMS compared with the model group, while reducing the expression levels of miR-135b-5p and further alleviating the depression-like behavior induced by CUMS. Concomitantly, the results indicated that the miR-135b-5p inhibitor inhibited CUMS-induced hippocampal cell apoptosis and significantly reduced the expression levels of cleaved caspase-3 and the ratio of cleaved caspase-3/caspase-3. Moreover, the miR-135b-5p inhibitor significantly reduced the CUMS-induced increase of the inflammatory factors IL-1ß, IL-6 and TNF-α in the hippocampal mouse samples, while significantly increasing the expression levels of SIRT1. Finally, the results demonstrated that all the effects of the miR-135b-5p inhibitor on CUMS-induced mice were significantly reversed by SIRT1 silencing. In conclusion, the present study indicated that the miR-135b-5p/SIRT1 pathway was a key mediator of antidepressant effects induced in depressed mice. Therefore, it could be considered a potential therapeutic target for the treatment of CUMS-induced depression.

Efficacy and Safety of Agomelatine vs Paroxetine Hydrochloride in Chinese Han Patients with Major Depressive Disorder: A Multicentre, Double-Blind, Noninferiority, Randomized Controlled Trial.

PURPOSE: The purpose of this study is to investigate the efficacy, safety, and tolerability of agomelatine and paroxetine in Chinese Han patients with major depressive disorder (MDD). METHODS: A 8-week, double-blind, randomized, parallel study was conducted in 14 medical centers in mainland China from December 2011 to September 2012. A total of 264 subjects with a primary Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition diagnosis of MDD were randomly assigned to receive agomelatine 25-50 mg/d (n = 132) or paroxetine 20-40 mg/d (n = 132). The primary efficacy was evaluated by the decrease of Hamilton Depression Rating Scale (HAM-D17) scores. The secondary measurements of efficacy included Hamilton Anxiety Rating Scale, Montgomery-Asberg Depression Rating Scale, Sheehan Disability Scale, Clinical Global Impressions-Severity, and Clinical Global Impressions-Improvement. The laboratory test abnormity, and observed and self-reported adverse events were all assessed as the measurements of safety and tolerability. RESULTS: Both the agomelatine and paroxetine groups showed significant improvement from baseline to the end point (P < 0.05) without between-group differences (P > 0.05). The mean decrease of HAM-D17 of agomelatine group was not inferior to the paroxetine group over the 8-week treatment (agomelatine 15.26 ± 6.44 vs paroxetine 14.87 ± 5.89, δ = 2.0; µA-µB 95% confidence interval, -1.13 to 1.91). The percentage of responders at the last postbaseline assessment was similar in the 2 groups on both HAM-D17 (agomelatine 66.15% vs paroxetine 63.49%) and Clinical Global Impressions-Improvement (agomelatine 79.09% vs paroxetine 80.36%). The anxiety (Hamilton Anxiety Rating Scale) and sleep symptoms (sleep items of HAM-D17) of the patients were improved significantly in the 2 groups at week 8 without between-group differences (P > 0.05). The incidence of overall adverse events was similar in the 2 groups (agomelatine 49.62% vs paroxetine 56.15%, P > 0.05). The incidence of adverse events in skin and subcutaneous tissue was higher in the paroxetine group than in the agomelatine group (none in agomelatine and 4.62% in paroxetine, P = 0.0144). CONCLUSIONS: Agomelatine showed equivalent antidepressant efficacy to paroxetine in treating MDD patients after 8 weeks of treatment with an acceptable safety.

[Progress of research on 5-hydroxymethylcytosine].

5-methylcytosine (5mC) in cytosine-guanine dinucleotide (CpG) is a usual epigenetic modification in mammals. It plays crucial roles in gene regulation, development, genomic imprinting and so on. In the last three years, it was discovered that in addition to 5mC, another modified cytosine base-5-hydroxymethylcytosine (5hmC) was abundant in many mammalian tissues, which may have different biological function from 5mC. This paper reviews the recent progresses in the studies of 5hmC.

Association study of VEGFA polymorphisms with schizophrenia in Han Chinese population.

Vascular endothelial growth factor A (VEGFA) has been implicated in neurotrophy and neurogenesis, which play a pivotal role in brain development and may be involved in the pathophysiology of schizophrenia (SCZ). We hypothesized that common genetic variants in the VEGFA gene may be associated with SCZ. In our study, seven tag single nucleotide polymorphisms (SNPs) within VEGFA were genotyped in 1034 SCZ patients and 952 healthy controls in the Han Chinese population. No significant differences of allele and genotype distributions of the 7 tag SNPs were identified between SCZ patients and healthy controls. The AA genotype of rs699947 nominally decreased the risk of SCZ in recessive inheritance model (p=0.03, OR=0.65, 95%CI=0.44-0.95, adjusted p=0.18). No significant associations were found between different haplotypes and the risk of SCZ (p>0.05). Our findings suggested that the selected tag SNPs of VEGFA may not confer a susceptibility of SCZ in the Han Chinese population.