Background. Recent studies suggest a correlation between the reduced Sirt-1 expression with Alzheimer’s diseases (AD) and depression, respectively, suggesting a possible pathogenic role of the altered Sirt-1 expression in neuronal degenerative diseases, such as AD and depression. However, the molecular mechanisms underlying how Sirt-1 reduction impairs neuronal functions remain unknown. Methods. We used the SK-N-SH neuroblastoma cells to study the role of Sirt-1 expression on physiological roles in neuronal cells. Gain of Sirt-1 was achieved by transiently transfecting Sirt-1 expression plasmid. Sirt-1-specific shRNA was used to elucidate the role of Sirt-1 loss of function. CCK-8 (Cell Counting Kit-8) assay and flow cytometry were used to evaluate cell proliferation. Semiquantitative western blotting was used to detect relative protein levels. A further luciferase reporter gene assay was employed to examine the effect of Sirt-1 expression on the transcriptional activity of p53. RT-qPCR was used to determine the mRNA levels of p21, Bax, and Bcl-2, which were the downstream target genes of p53. Results. Sirt-1 suppressed the p53 downstream gene p21 transcription, while shRNA-mediated Sirt-1 knockdown resulted in a significant increase in p21 expression, implying a possibility that Sirt-1 promotes neuron proliferation through suppressing p53 transcriptional activity. The mRNA and protein levels of p53 were not affected by the altered Sirt-1 expression, suggesting that Sirt-1 regulates the transcriptional regulatory activity of p53 rather than p53 expression. Indeed, we further confirmed that Sirt-1 appeared to inhibit p53 transcriptional activity by attenuating its acetylation and resulted in a decrease of p53’s binding to the p21 promoter. Overexpressed Sirt-1 scavenged reactive oxygen species (ROS) production in SK-N-SH with H2O2. Knockdown of Sirt-1 presented opposite effect; the addition of EX527 (Sirt-1 inhibitor) increased ROS accumulation. Conclusions. Oxidative stress induces Sirt-1 in neuron cells, and Sirt-1 promotes proliferation in SK-N-SH cells, which protects them from oxidative stress-induced cell death, potentially via suppressing the transcriptional activity of p53. These results provide a molecular explanation underlying how the reduced Sirt-1 potentially causes the AD and depression-related diseases, supporting the idea that Sirt-1 can possibly be used as a diagnostic biomarker and/or therapeutic drug target for the AD and depression-related diseases.

Objective. This paper aimed to probe changes in the default mode network (DMN) functional connectivity (DMNFC) of the brain of patients with insomnia disorder (ID) under the resting state. Methods. A total of 67 patients with ID and 67 graphically matched healthy controls were selected. Then, their general information was collected, followed by a psychological scale valuation. Resting state functional magnetic resonance imaging (rs-fMRI) scanning was conducted. Subsequently, collected statistics were processed, bilateral precuneus and medial superior frontal gyrus were defined as regions of interest (ROI), and the difference in intensity between these two groups was compared. Results. Compared with the healthy control group, the patients in the ID group were observed with abnormalities of DMNFC. Specifically, a significant increase in the functional connectivity (FC) could be observed between the left medial superior frontal gyrus and left central anterior gyrus, the left medial superior frontal gyrus and anterior cingulate gyrus, the right medial superior frontal gyrus and left central anterior gyrus, the left anterior cuneiform and left central anterior/posterior gyrus, the left anterior cuneiform and left superior occipital gyrus, as well as the right anterior cuneiform and left central posterior gyrus. However, the FC between the left anterior cuneiform and the right middle frontal gyrus was weakened, as well as between the left anterior cuneiform and the right angle gyrus and between the right precuneus and the left inferior temporal gyrus. Conclusion. ID patients may suffer changes in FC. The decline of FC in DMN may be one of the underlying causes of ID; the enhancement of FC between DMN and the visual-spatial attention network may play a key role in the mechanisms of impaired brain functional networks of ID.

A significant association between major depressive disorder (MDD) and restless legs syndrome (RLS), but RLS prevalence is dramatically different among MDD individuals across studies. Our present work aimed to comprehensively evaluate available evidences to determine the role of RLS in MDD. PubMed, Web of Science, Embase, Science Online, Wip Chinese Biomedical Journal, Wanfang and Chinese National Knowledge Infrastructure were searched to identify observational and case-control studies relevant to RLS and MDD. Stata 12.0 software was used for meta-analysis. RLS individuals exhibited a higher risk of MDD than non-RLS controls (OR 2.05, 95%CI 1.80–2.33; p<0.05). No significant differences were found in MDD prevalence between young RLS patients (OR 2.10, 95%CI 1.72–2.56) and older RLS patients (OR 2.02, 95%CI 1.70–2.39). In addition, no significant difference in MDD prevalence was evident between between Asian (OR 1.98, 95%CI 1.66–2.37) and European or American (OR 1.76, 95%CI 1.54–2.01) RLS patients. Our meta-analysis provides evidence that the risk for MDD is higher among RLS patients compared to non-RLS individuals suggesting that RLS may play an important role in MDD patheogenesis.