Zhi-Qing David Xu

A Neuropeptide Y Variant (rs16139) Associated with Major Depressive Disorder in Replicate Samples from Chinese Han Population

Objective This study aimed to investigate the single nucleotide polymorphisms (SNPs) of neuropeptide Y (NPY) and major depressive disorder (MDD) in Chinese Han population. Design Prospective and randomized studies were carried out. Patients A total of 700 patients (324 male and 376 female; mean age = 40±14.9 years) with depression who met the diagnostic criteria of Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) and 673 healthy controls (313 male and 360 female; mean age = 41.9±17.2 years) were used to investigate the relationship between SNPs of NPY and the pathogenesis of MDD. A total of 417 patients (195 male and 202 female; mean age = 36±14.2 years) diagnosed with MDD and 314 healthy controls (153 male and 161 female; mean age = 37.9±14.2 years) from Chinese Han population were used to verify the relationship between SNPs of NPY and the pathogenesis of MDD. Intervention and outcome Ligase detection reactions were performed to detect the SNP sites of NPY. A series of statistical methods was carried out to investigate the correlation between the NPY gene SNP and MDD. Results Statistical analysis showed a significant correlation between the SNP sites rs16139 in NPY and the morbidity of depression. Patients with MDD have a lower frequency of A-allele in rs16139 in replicate samples from Chinese Han population. However, the frequency varied between male and female patients. Conclusion The gene polymorphism loci rs16139 was closely related to MDD in Chinese Han population.

Association of Galanin and Major Depressive Disorder in the Chinese Han Population

Objective This study aimed to investigate the association of galanin (GAL) gene and the development of depression in the Chinese Han population. Methods A total of 700 patients with depression who met the diagnostic criteria of Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) and 673 healthy controls were used in this study. Ligase detection reactions were performed on 10 selected single nucleotide polymorphism (SNP) sites in the GAL gene. A series of statistical methods were carried out to investigate the correlation between the GAL gene SNP and the patient susceptibility to depression. Results The SNPs of rs694066 in the GAL gene showed a positive correlation with MDD. Compared with the healthy controls, lower frequency of G/G genotype and higher frequency of A/G genotype were observed in rs694066 in MDD patients, a lower frequency of G-allele and higher frequency of A-allele were observed in rs694066. These correlations were more pronounced in the 376 female patients and 360 female control subjects than in the 324 male patients and 313 healthy male subjects. Conclusions This study investigated the relationship between the GAL gene SNP and the susceptibility to depression in the Chinese Han population. The findings clearly indicate that the GAL gene polymorphism is closely correlated to the incidence of depression in the Chinese Han female patients.

PLASMA GALANIN IS A BIOMARKER FOR SEVERITY OF MAJOR DEPRESSIVE DISORDER

Objective: This study investigated the association between plasma galanin level and depression severity. Methods: The severity of depression symptoms of 79 patients with major depressive disorder (MDD; 52 women and 27 men, 71 patients in onset, 8 in remission) was assessed using the 17-item Hamilton Depression Rating Scale. Venous fasting blood samples (5 mL) were taken from the 79 MDD patients, 35 healthy siblings, and 19 healthy controls, and plasma samples were prepared. Galanin levels in the plasma were measured by radioimmunoassay. Results: Plasma galanin in MDD patients was significantly higher than that of remission patients, healthy siblings, or healthy controls (P < 0.05) There was no significant difference between the healthy sibling and healthy control groups (P = 0.924). Plasma galanin of remission patients was also significantly higher than that of healthy controls (P < 0.05). There was no significant correlation between age and galanin levels in the 79 patients (r = 0.053, P = 0.646), nor was there a correlation between age and galanin levels when patients were stratified by gender (P > 0.05). There was a significant positive correlation between plasma galanin levels and depression severity in women MDD patients (r = 0.329, df = 42, P = 0.020), but not in men patients. Conclusions: Plasma galanin levels may be an important biomarker for depression severity, especially in female patients.

Characterization of the Rat GAL2R Promoter: Positive Role of ETS-1 in Regulation of the Rat GAL2R Gene in PC12 Cells

Galanin receptor 2 (GAL2R) is a G protein-coupled receptor for the neuropeptide galanin that regulates many important physiological functions and pathological processes. To investigate the molecular mechanism governing GAL2R gene transcription, the rat GAL2R promoter was isolated and analyzed. We found that the region from −320 to −300 of the GAL2R promoter contains two putative ETS-1 elements and plays an important role in regulating GAL2R promoter activity. We also showed that transcription factor ETS-1 bound to this region in vitro and in vivo. Overexpression of ETS-1 significantly increased GAL2R promoter activity and transcription of the GAL2R gene, whereas knockdown of ETS-1 produced the opposite effects. In addition, we showed that ETS-1 recruited co-activator p300 to the GAL2R promoter. These data indicate a role for ETS-1 in the control of the GAL2R gene expression and provide a basis for understanding the transcriptional regulation of the GAL2R gene.

Resveratrol Represses Pokemon Expression in Human Glioma Cells

POK erythroid myeloid ontogenic factor (Pokemon), an important proto-oncoprotein, is a transcriptional repressor that regulates the expression of many genes and plays an important role in tumorigenesis. Resveratrol (RSV), a natural polyphenolic compound, has many beneficial biological effects on health. In this study, we investigated the role of Pokemon in RSV-induced biological effects and the effect of RSV on the expression of Pokemon in glioma cells. We found that overexpression of Pokemon decreased RSV-induced cell apoptosis, senescence, and anti-proliferative effects. Moreover, we showed that RSV could efficiently decrease the activity of the Pokemon promoter and the expression of Pokemon. Meanwhile, RSV also inhibited Sp1 DNA binding activity to the Pokemon promoter; whereas, it did not influence the expression and nuclear translocation of Sp1. In addition, we found that RSV could increase the recruitment of HDAC1, but decreased p300 to the Pokemon promoter. Taken together, all these results extended our understanding on the anti-cancer mechanism of RSV in glioma cells.

Pokemon (FBI-1) interacts with Smad4 to repress TGF-β-induced transcriptional responses.

Pokemon, an important proto-oncoprotein, is a transcriptional repressor that belongs to the POK (POZ and Krüppel) family. Smad4, a key component of TGF-β pathway, plays an essential role in TGF-β-induced transcriptional responses. In this study, we show that Pokemon can interact directly with Smad4 both in vitro and in vivo. Overexpression of Pokemon decreases TGF-β-induced transcriptional activities, whereas knockdown of Pokemon increases these activities. Interestingly, Pokemon does not affect activation of Smad2/3, formation of Smads complex, or DNA binding activity of Smad4. TGF-β1 treatment increases the interaction between Pokemon and Smad4, and also enhances the recruitment of Pokemon to Smad4-DNA complex. In addition, we also find that Pokemon recruits HDAC1 to Smad4 complex but decreases the interaction between Smad4 and p300/CBP. Taken together, all these data suggest that Pokemon is a new partner of Smad4 and plays a negative role in TGF-β pathway.

Lack of association between dendritic cell nuclear protein-1 gene and major depressive disorder in the Han Chinese population

OBJECTIVES Dendritic cell nuclear protein-1 (DCNP1) has been associated with major depressive disorder (MDD) based on analysis of a population of patients in the United Kingdom. In the present study we have investigated a possible role of DCNP in MDD in the Han Chinese population, including a meta-analysis of different ethnic populations. METHODS Eight single nucleotide polymorphisms (SNPs) spanning the entire DCNP1 were carefully selected, genotyped and used for the SNP and haplotype analyses in 574 patients with MDD and 642 healthy controls. Considering the potential genetic association difference across different ethnic populations, we further conducted a meta-analysis for Chinese and European populations. RESULTS rs10061623 showed initial association with MDD in females in the allele analysis (p-value: 0.043). However, this association did not remain significant after Bonferroni correction to adjust for multiple comparisons (corrected p-value: 0.344). Other single-marker and haplotype analyses did not reveal any significant differences between patients and controls. The SNP (rs12520799), positive in the original UK study, gave negative results in all our analyses. The meta-analysis results of rs12520799 also suggested possible negative association between this SNP and MDD in the Han Chinese population. CONCLUSIONS In the Han Chinese population, common DCNP1 polymorphisms are unlikely to be important in the genetic susceptibility to MDD.

Within-subject test-retest reliability of the atlas-based cortical volume measurement in the rat brain: A voxel-based morphometry study

BACKGROUND Various neurological and psychological disorders are related to cortical volume changes in specific brain regions, which can be measured in vivo using structural magnetic resonance imaging (sMRI). There is an increasing interest in MRI studies using rat models, especially in longitudinal studies of brain disorders and pharmacologic interventions. However, morphometric changes observed in sMRI are only meaningful if the measurements are reliable. To date, a systematic evaluation of the test-retest reliability of the morphometric measures in the rat brain is still lacking. NEW METHOD We rigorously evaluated the test-retest reliability of morphometric measures derived from the voxel-based morphometry (VBM) analysis. 37 Sprague-Dawley rats were scanned twice at an interval of six hours and the gray matter volume was estimated using the VBM-DARTEL method. The intraclass coefficient, percent volume change and Pearson correlation coefficient were used to evaluate the reliability in 96 subregions of the rat brain. RESULTS Most subregions showed excellent test-retest reliabilities within an interval of 6 h while a few regions demonstrated lower reliability, especially in the retrosplenial granular cortex. The results were consistent between different methods of reliability assessment. COMPARISON WITH EXISTING METHOD To the best of our knowledge, this is the first study to quantify the test-retest reliability of the VBM measurements of the rat brain. CONCLUSION Atlas-based cortical volume of the rat brain can be reliably estimated using the VBM-DARTEL method in most subregions. However, findings in subregions with lower reliability must be interpreted with caution.

Pokemon decreases the transcriptional activity of RARα in the absence of ligand.

Abstract Pokemon is a transcriptional repressor that belongs to the POZ and Krüppel (POK) protein family. In this study, we investigated the potential interaction between Pokemon and retinoic acid receptor alpha (RARα) and determined the role of Pokemon in regulation of RARα transcriptional activity in the absence of ligand. We found that Pokemon could directly interact with RARα. Moreover, we demonstrated that Pokemon could decrease the transcriptional activity of RARα in the absence of ligand. Furthermore, we showed that Pokemon could repress the transcriptional activity of RARα by increasing the recruitment of nuclear receptor co-repressor (NCoR) and silencing mediator of retinoic acid and thyroid hormone receptor (SMRT) to the retinoic acid response element (RARE) element. Taken together, these data suggest that Pokemon is a novel partner of RARα that acts as a co-repressor to regulate RARα transcriptional activity in the absence of ligand.

Erratum to: Resveratrol Represses Pokemon Expression in Human Glioma Cells

Jiajun Cui and Anne-Marie Overstreet of Department of Cancer and Cell Biology, University of Cincinnati (UC), OH, USA contributed to paper writing and experimental design thus they were listed as co-authors of the paper. However, the Department of Cancer and Cell Biology of UC indicated that it may not be appropriate to include the Department of UC as an affiliating institute based on the following considerations: