Chongqing Key Laboratory of Neurobiology

Chongqing, China

Chongqing Key Laboratory of Neurobiology

Chongqing, China
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Han X.,Chongqing Medical University | Han X.,Chongqing Key Laboratory of Neurobiology | Shao W.,Chongqing Medical University | Shao W.,Chongqing Key Laboratory of Neurobiology | And 14 more authors.
Neuroscience | Year: 2015

Major depressive disorder (MDD) is a prevalent psychiatric mood illness and a major cause of disability and suicide worldwide. However, the underlying pathophysiology of MDD remains poorly understood due to its heterogenic nature. Extensive pre-clinical research suggests that many molecular alterations associated with MDD preferentially localize to the postsynaptic density (PSD). Here, we used a rodent chronic mild stress (CMS) model to generate susceptible and unsusceptible subpopulations. Proteomic analysis using an isobaric tag for relative and absolute quantitation (iTRAQ) and tandem mass spectrometry was performed to identify differentially expressed proteins in enriched PSD preparations from the hippocampi of different groups. More than 1500 proteins were identified and quantified, and 74 membrane proteins were differentially expressed. Of these membrane proteins, 51 (69%) were identified by SynaptomeDB search as having a predicted PSD localization. The unbiased profiles identified several PSD candidate proteins that may be related to CMS vulnerability or insusceptibility, and these two CMS phenotypes displayed differences in the abundance of several types of proteins. A detailed protein functional analysis pointed to a role for PSD-associated proteins involved in signaling and regulatory functions. Within the PSD, the N-methyl-. d-aspartate (NMDA) receptor subunit NR2A and its downstream targets contribute to CMS susceptibility. Further analysis of disease relevance indicated that the PSD contains a complex set of proteins of known relevance to mental illnesses including depression. In sum, these findings provide novel insights into the contribution of PSD-associated proteins to stress susceptibility and further advance our understanding of the role of hippocampal synaptic plasticity in MDD. © 2015 IBRO.


PubMed | Chongqing Medical University, Southwest University and Chongqing Key Laboratory of Neurobiology
Type: | Journal: Scientific reports | Year: 2016

Major depressive disorder is associated with abnormal anatomical and functional connectivity, yet alterations in whole cortical thickness topology remain unknown. Here, we examined cortical thickness in medication-free adult depression patients (n=76) and matched healthy controls (n=116). Inter-regional correlation was performed to construct brain networks. By applying graph theory analysis, global (i.e., small-worldness) and regional (centrality) topology was compared between major depressive disorder patients and healthy controls. We found that in depression patients, topological organization of the cortical thickness network shifted towards randomness, and lower small-worldness was driven by a decreased clustering coefficient. Consistently, altered nodal centrality was identified in the isthmus of the cingulate cortex, insula, supra-marginal gyrus, middle temporal gyrus and inferior parietal gyrus, all of which are components within the default mode, salience and central executive networks. Disrupted nodes anchored in the default mode and executive networks were associated with depression severity. The brain systems involved sustain core symptoms in depression and implicate a structural basis for depression. Our results highlight the possibility that developmental and genetic factors are crucial to understand the neuropathology of depression.


Wei Y.,Chongqing Medical University | Wei Y.,Chongqing Key Laboratory of Neurobiology | Zou D.,Chongqing Medical University | Zou D.,Chongqing Key Laboratory of Neurobiology | And 4 more authors.
Nutrition | Year: 2015

Objective: Epidemiologic studies evaluating the association between processed meat and red meat consumption and glioma risk have produced inconsistent results. Thus, the aim of this study was to conduct a meta-analysis to test the hypothesis that high levels of processed meat consumption could increase the risk for glioma. Methods: Pertinent studies were identified by a search of PubMed and Web of Knowledge up to February 2014. Random-effects model was used to combine the results. Publication bias was estimated using Egger's regression asymmetry test. Results: Fourteen studies involving 3641 cases about processed meat consumption and 3 studies involving 1156 cases about red meat consumption with risk for glioma were included in this meta-analysis. The combined relative risk (RR) of glioma associated with processed meat consumption was 1.25 (95% confidence interval [CI], 1.08-1.45) overall, and 1.28 (95% CI, 1.09-1.50) in the United States. For subgroup of study design, significant association was also found in case-control studies (RR, 1.33; 95% CI, 1.09-1.62), but not in the cohort studies. The association was not significant between red meat consumption and glioma risk (summary RR, 0.89; 95% CI, 0.71-1.12). No publication biases were found. Conclusions: Our analysis indicated that high levels of processed meat consumption might increase the risk for glioma, and findings are consistent with the hypothesis. No association was found between red meat consumption and glioma risk. © 2015 Elsevier Inc.


Liu X.,Chongqing Medical University | Liu X.,Chongqing Key Laboratory of Neurobiology | Zhang L.,Chongqing Medical University | Zhang L.,Chongqing Key Laboratory of Neurobiology | And 8 more authors.
Journal of Affective Disorders | Year: 2014

Background Mounting evidence has demonstrated microRNA involvement in the set of diverse pathways associated with major depressive disorder (MDD). Reverse transcription quantitative real-time PCR (RT-qPCR) has been widely used in microRNA expression studies. To achieve accurate and reproducible microRNA RT-qPCR data, reference genes are required. The goal of this study is to systematically identify suitable reference genes for normalizing RT-qPCR assays of microRNA expression in the plasma of MDD patients. Methods Candidate reference genes were selected from plasma samples of both MDD and healthy controls by miRNA microarrays, in addition to a frequently used reference gene - U6 small nuclear RNA. Putative reference genes were thereafter validated by RT-qPCR in plasma samples, and analyzed by the four statistical algorithms geNorm, NormFinder, BestKeeper and the comparative delta-Ct method. Finally, the validity of the selected reference genes was assessed with two significantly decreased miRNAs identified by microarray. Results Five miRNAs (miR-320d, miR-101-3p, miR-106a-5p, miR-423-5p, miR-93-5p) based on microarray data and U6 were identified as putative reference genes. The results of the merged data from four statistical algorithms revealed that the most adequate microRNAs tested for normalization were miR-101-3p and miR-93-5p. Assessment of the validity of the selected reference genes confirms the suitability of applying the combination of miR-101-3p and miR-93-5p as optimal references genes. Limitations Relatively small sample size; and lack of other disease groups. Conclusions The normalization methods proposed here can contribute to improve studies on MDD biomarker identification and/or pathogenesis by providing more reliable and accurate expression measurements. © 2014 Published by Elsevier B.V. All rights reserved.


Zhang K.,Chongqing Key Laboratory of Neurobiology | Zhang K.,Chongqing Medical University | Zhang Y.,Chongqing Key Laboratory of Neurobiology | Zhang Y.,Chongqing Medical University | And 4 more authors.
International Journal of Oncology | Year: 2014

MicroRNAs (miRNAs) are non-coding single-stranded RNAs in eukaryotes and are involved in the regulation of the post-transcriptional expression of specific genes. Studies have demonstrated that miRNAs play important roles in regulating diverse physiological events such as cell proliferation, differentiation and embryo development. In recent decades, considerable attention has been given to the relationship between miRNA and the pathology of cancers, particularly breast cancer. A large number of miRNAs have been shown to be involved in the pathophysiology of breast cancer. Studies have revealed that some miRNAs might regulate the oncogenesis and growth of breast cancer by acting on breast tumor-initiating cells or other downstream targets. Studies have also demonstrated that some miRNAs act as suppressors of metastasis or promoters of breast cancer. Additionally, certain miRNAs are involved in cancer tissue angiogenesis (one of the most important mechanisms of tumor growth and metastasis). Clinical evidence indicates that some miRNAs can be used as diagnostic and prognostic biomarkers for breast cancer due to their significantly increased or decreased expression in cancer tissue. Moreover, certain miRNAs may have therapeutic potential for targeting ER-α/HER, breast tumor-initiating cells and metastasis as well as multidrug resistance. In this review, we discuss the relationship between miRNAs and the pathogenesis of breast cancer as well as the progress of current research on the miRNA-specific diagnosis, prognosis and treatment of breast cancer.


Huang P.,Chongqing Medical University | Huang P.,Chongqing Key Laboratory of Neurobiology | Qiu L.,University of Sichuan | Shen L.,Chongqing Medical University | And 8 more authors.
Human Brain Mapping | Year: 2013

As a complex mental process, creativity requires the coordination of multiple brain regions. Previous pathological research on figural creativity has indicated that there is a mechanism by which the left side of the brain inhibits the activities of the right side of the brain during figural creative thinking, but this mechanism has not been directly demonstrated. In this study, we used functional magnetic resonance imaging (fMRI) to demonstrate the existence of this inhibitory mechanism in young adults (15 women, 11 men, mean age: 22 years) that were not artists. By making comparisons between brain activity during creative and uncreative tasks, we found increased activity in the left middle and inferior frontal lobe and strong decreases in activity in the right middle frontal lobe and the left inferior parietal lobe. As such, these data suggest that the left frontal lobe may inhibit the right hemisphere during figural creative thinking in normal people. Moreover, removal of this inhibition by practicing artistry or through specific damage to the left frontal lobe may facilitate the emergence of artistic creativity. © 2012 Wiley Periodicals, Inc.


Zheng P.,Chongqing Medical University | Zheng P.,Chongqing Key Laboratory of Neurobiology | Wang Y.,Chongqing Medical University | Wang Y.,Chongqing Key Laboratory of Neurobiology | And 15 more authors.
Molecular and Cellular Proteomics | Year: 2013

Major depressive disorder (MDD) is a widespread and debilitating mental disorder. However, there are no biomarkers available to aid in the diagnosis of this disorder. In this study, a nuclear magnetic resonance spectroscopy-based metabonomic approach was employed to profile urine samples from 82 first-episode drug-naïve depressed subjects and 82 healthy controls (the training set) in order to identify urinary metabolite biomarkers for MDD. Then, 44 unselected depressed subjects and 52 healthy controls (the test set) were used to independently validate the diagnostic generalizability of these biomarkers. A panel of five urinary metabolite biomarkers-malonate, formate, N-methylnicotinamide, mhydroxyphenylacetate, and alanine-was identified. This panel was capable of distinguishing depressed subjects from healthy controls with an area under the receiver operating characteristic curve (AUC) of 0.81 in the training set. Moreover, this panel could classify blinded samples from the test set with an AUC of 0.89. These findings demonstrate that this urinary metabolite biomarker panel can aid in the future development of a urine-based diagnostic test for MDD. © 2013 by The American Society for Biochemistry and Molecular Biology, Inc.


PubMed | Chongqing Medical University and Chongqing Key Laboratory of Neurobiology
Type: Journal Article | Journal: Neurochemical research | Year: 2016

Hypothalamus-pituitary-adrenal (HPA) axis hyperactivity is observed in many patients suffering from depression. However, the mechanism underlying the dysfunction of the HPA axis is not well understood. Moreover, dysfunction of the hypothalamus, the key brain region of the HPA axis, has not been well-explored. The aim of our study was to examine possible alterations in hypothalamus protein expression in a model of depression using proteomic analysis. In order to achieve this aim, mice were exposed to chronic unpredictable mild stress (CUMS), as the paradigm results in hyperactivity of the HPA axis. Differential protein expression between the hypothalamic proteomes of CUMS and control mice was then assessed through two-dimensional electrophoresis followed by matrix-assisted laser desorption ionization-time of flight-tandem mass spectrometry. Thirty-seven proteins with a threshold of a 1.5-fold change and a p value 0.05 were identified as being differentially expressed between CUMS and control mice, and were quantified for bioinformatics analysis. Glycometabolism, citrate cycle (TCA cycle) and oxidation respiratory chain were found to have changed significantly. Glial fibrillary acidic protein and glutamine synthetase were further validated by Western Blot. Our results demonstrated that CUMS mice exhibited a dramatic protein change both in glutamate metabolism and energy mobilization, which may shed some light on the role of the hypothalamus in the pathology of stress-induced depression.


PubMed | Chongqing Medical University and Chongqing Key Laboratory of Neurobiology
Type: Journal Article | Journal: Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologicas | Year: 2016

New generation antidepressant therapies, including serotonin-norepinephrine reuptake inhibitor (SNRIs), were introduced in the late 1980s; however, few comprehensive studies have compared the benefits and risks of various contemporary treatments for major depressive disorder (MDD) in young patients. A comprehensive literature search of PubMed, Cochrane, Embase, Web of Science, and PsycINFO databases was conducted from 1970 to January 2015. Only clinical trials that randomly assigned one SNRI or placebo to patients aged 7 to 18 years who met the diagnostic criteria for major depressive disorder were included. Treatment success, dropout rate, and suicidal ideation/attempt outcomes were measured. Primary efficacy was determined by pooling the risk ratios (RRs) of treatment response and remission. Acceptability was determined by pooling the RRs of dropouts for all reasons and for adverse effects as well as suicide-risk outcomes. Five trials with a total of 973 patients were included. SNRIs were not significantly more effective than placebo for treatment response but were for remission. The comparison of patients taking SNRIs that dropped out for all reasons and those taking placebo did not reach statistical significance. Significantly more patients taking SNRIs dropped out for adverse effects than those taking placebo. No significant difference was found in suicide-related risk outcomes. SNRI therapy does not display a superior efficacy and is not better tolerated compared to placebo in these young patients. However, duloxetine has a potential beneficial effect for depression in young populations, showing a need for further research.

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