HIV-1 Tat and methamphetamine co-induced oxidative cellular injury is mitigated by N-acetylcysteine amide (NACA) through rectifying mTOR signaling.

Methamphetamine (Meth) is an addictive psychostimulant whose abuse is intimately linked to increased risks for HIV-1 infection. Converging lines of evidence indicate that Meth also aggravates the symptoms of HIV-associated neurocognitive disorders (HAND), though the underlying mechanisms remain poorly understood. By using the lipophilic antioxidant N-acetylcysteine amide (NACA) as an interventional agent, we examined the roles of oxidative stress in autophagy and apoptosis induced by HIV-Tat (the transactivator of transcription), Meth or their combined treatment in human SH-SY5Y neuroblastoma cells and in the rat striatum. Oxidative stress was monitored in terms of the production of intracellular reactive oxygen species (ROS) and antioxidant reserves including glutathione peroxidase (GPx) and Cu,Zn-superoxide dismutase (SOD). NACA significantly reduced the level of ROS and restored GPx and SOD to levels comparable to that of normal control, implying a cytoprotective effect of NACA against oxidative stress elicited by Tat- and/or Meth. Protein expression of mammalian target of rapamycin (mTOR) was measured in SH-SY5Y cells and in the rat striatum to further explore the underlying mechanism of NACA protect against oxidative stress. The results support a beneficial effect of NACA in vivo and in vitro through rectification of the mTOR signaling pathway. Collectively, our study shows that NACA protects against Meth and/or Tat-induced cellular injury in vitro and in the rat striatum in vivo by attenuating oxidative stress, apoptosis and autophagy, at least in part, via modulation of mTOR signaling.

[Synthesis and antifungal activities of N-1,3,4-thiadiazol-2-yl-4-oxo-thiochroman-2-yl-formamide derivatives].

Thiochromanones and 1,3,4-thiadiazoles as heterocyclic compounds have broad biological activities. In order to find novel compounds with antifungal bioactivity, substituted thiophenol and maleic anhydride were used to synthesize the intermediate 4-oxothiochromane-2-carboxylic acid. It was reacted with 2-amino-1,3,4-thiadiazole to get fourteen target compounds containing 1,3,4-thiadiazole moiety. The structures of the obtained compounds were confirmed by 1H NMR, 13C NMR and HR-MS. All compounds were investigated for antifungal activity via microdilution broth method. The results showed that the target compounds 3a and 3c to Epidermophyton floccosum and Mucor racemosus exhibited better antifungal activity than the positive control fluconazole, in which the minimum inhibition concentration can reach 8 µg·mL−1 and 16 µg·mL−1. Compound 3e showed significant inhibitory activity to Helminthosporium maydis, Sclerotinia sclerotiorum and Botrytis cinerea compared with that of the positive control carbendazim. Compound 3b exhibited inhibitory activity to Helminthosporium maydis better than the positive control carbendazim.

Synthesis, Characterization and Antifungal Evaluation of Novel Thiochromanone Derivatives Containing Indole Skeleton.

Invasive fungal disease constitutes a growing health problem and development of novel antifungal drugs with high potency and selectivity against new fungal molecular targets are urgently needed. In order to develop potent antifungal agents, a novel series of 6-alkyl-indolo[3,2-c]-2H-thiochroman derivatives were synthesized. Microdilution broth method was used to investigate antifungal activity of these compounds. Most of them showed good antifungal activity in vitro. Compound 4o showed the best antifungal activity, which (inhibition of Candida albicans and Cryptococcus neoformans) can be achieved at the concentration of 4 µg/mL. Compounds 4b (inhibition of Cryptococcus neoformans), 4j (inhibition of Cryptococcus neoformans), 4d (inhibition of Candida albicans) and 4h (inhibition of Candida albicans) also showed the best antifungal activity at the concentrations of 4 µg/mL. The molecular interactions between 4o and the N-myristoyltransferase of Candida albicans (PDB ID: 1IYL) were finally investigated through molecular docking. The results indicated that these thiochromanone derivatives containing indole skeleton could serve as promising leads for further optimization as novel antifungal agents.

Touch DNA of shed skin cells from the deployed airbag to address drunken driving crimes.

In the criminal cases of driving under the influence (DUI), DNA evidence can be collected from the deployed airbag of the motor vehicle and submitted to the crime lab for touch DNA analysis. The evidence can be acquired when the skin cells are observed on the surface of the airbag in a traffic accident. However, the low quantity or quality of the evidence collected from a crime scene prevents further identification analysis in many cases. In the current study, we reported a case of identifying touch DNA extraction from the shed skin cells from the deployed airbag of a motor vehicle. We managed to collect DNA evidence from the shed skin cells in an airbag using a proper approach of collection and extraction. The 5.87 ng of extracted DNA was sufficient for genotyping and forensic identification, which helped to identify the driver of the car in collision with a pier in the street. In DUI cases and other traffic accidents, therefore, the amount of touch DNA extracted from the deployed airbag can be sufficient for DNA marker genotyping and further analysis.

Association study identifying a new susceptibility gene (AUTS2) for schizophrenia.

Schizophrenia (SCZ) is a severe and debilitating mental disorder, and the specific genetic factors that underlie the risk for SCZ remain elusive. The autism susceptibility candidate 2 (AUTS2) gene has been reported to be associated with autism, suicide, alcohol consumption, and heroin dependence. We hypothesized that AUTS2 might be associated with SCZ. In the present study, three polymorphisms (rs6943555, rs7459368, and rs9886351) in the AUTS2 gene were genotyped in 410 patients with SCZ and 435 controls using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and forced PCR-RFLP methods. We detected an association between SCZ and the rs6943555 genotype distribution (odds ratio (OR)=1.363, 95% confidence interval (CI): 0.848-2.191, p=0.001). The association remained significant after adjusting for gender, and a significant effect (p=0.001) was observed among the females. In the present study, rs6943555 was determined to be associated with female SCZ. Our results confirm previous reports which have suggested that rs6943555 might elucidate the pathogenesis of schizophrenia and play an important role in its etiology.

A functional polymorphism in IL-1A gene is associated with a reduced risk of gastric cancer.

Accumulating evidence has identified that polymorphism residing in the microRNA (miRNA) binding site of target genes can affect the strength of miRNA binding and influence individual susceptibility to cancer. Recently, an insertion/deletion polymorphism (rs3783553 ttca/-) at miRNA-122 binding site in the interleukin-1A 3' untranslated region has been demonstrated to be functional. We aimed to investigate the association between the rs3783553 polymorphism and the risk of gastric cancer (GC). We genotyped the rs3783553 polymorphism in 207 GC patients and 381 healthy controls by using a polymerase chain reaction method. We found that the ins/ins (ttca/ttca) genotype of the rs3783553 polymorphism was associated with a significantly decreased risk of GC (P = 0.02, odds ratio = 0.48, 95% confidence interval 0.26-0.90). This finding suggests that the rs3783553 polymorphism may be a protective factor for the development of GC.

Dopamine D1 receptor gene variation modulates opioid dependence risk by affecting transition to addiction.

Dopamine D1 receptor (DRD1) modulates opioid reinforcement, reward, and opioid-induced neuroadaptation. We propose that DRD1 polymorphism affects susceptibility to opioid dependence (OD), the efficiency of transition to OD, and opioid-induced pleasure response. We analyzed potential association between seven DRD1 polymorphisms with the following traits: duration of transition from the first use to dependence (DTFUD), subjective pleasure responses to opioid on first use and post-dependence use, and OD risk in 425 Chinese with OD and 514 healthy controls. DTFUD and level of pleasure responses were examined using a semi-structured interview. The DTFUD of opioid addicts ranged from 5 days to 11 years. Most addicts (64.0%) reported non-comfortable response upon first opioid use, while after dependence, most addicts (53.0%) felt strong opioid-induced pleasure. Survival analysis revealed a correlation of prolonged DTFUD with the minor allele-carrying genotypes of DRD1 rs4532 (hazard ratios (HR) = 0.694; p = 0.001) and rs686 (HR = 0.681, p = 0.0003). Binary logistic regression indicated that rs10063995 GT genotype (vs. GG+TT, OR = 0.261) could predict decreased pleasure response to first-time use and the minor alleles of rs686 (OR = 0.535) and rs4532 (OR = 0.537) could predict decreased post-dependence pleasure. Moreover, rs686 minor allele was associated with a decreased risk for rapid transition from initial use to dependence (DTFUD≤30 days; OR = 0.603) or post-dependence euphoria (OR = 0.603) relative to major allele. In conclusion, DRD1 rs686 minor allele decreases the OD risk by prolonging the transition to dependence and attenuating opioid-induced pleasure in Chinese.

Suppression of neuroinflammation by astrocytic dopamine D2 receptors via αB-crystallin.

Chronic neuroinflammation is a common feature of the ageing brain and some neurodegenerative disorders. However, the molecular and cellular mechanisms underlying the regulation of innate immunity in the central nervous system remain elusive. Here we show that the astrocytic dopamine D2 receptor (DRD2) modulates innate immunity through αB-crystallin (CRYAB), which is known to suppress neuroinflammation. We demonstrate that knockout mice lacking Drd2 showed remarkable inflammatory response in multiple central nervous system regions and increased the vulnerability of nigral dopaminergic neurons to neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced neurotoxicity. Astrocytes null for Drd2 became hyper-responsive to immune stimuli with a marked reduction in the level of CRYAB. Preferential ablation of Drd2 in astrocytes robustly activated astrocytes in the substantia nigra. Gain- or loss-of-function studies showed that CRYAB is critical for DRD2-mediated modulation of innate immune response in astrocytes. Furthermore, treatment of wild-type mice with the selective DRD2 agonist quinpirole increased resistance of the nigral dopaminergic neurons to MPTP through partial suppression of inflammation. Our study indicates that astrocytic DRD2 activation normally suppresses neuroinflammation in the central nervous system through a CRYAB-dependent mechanism, and provides a new strategy for targeting the astrocyte-mediated innate immune response in the central nervous system during ageing and disease.

Enhanced protective immune response to PCV2 subunit vaccine by co-administration of recombinant porcine IFN-γ in mice.

The capsid (Cap) protein of PCV2 is the major immunogenic protein that is crucial to induce PCV2-specific neutralizing antibodies and protective immunity; thus, it is a suitable target antigen for the research and development of genetically engineered vaccines against PCV2 infection. IFN-γ has exhibited potential efficacy as an immune adjuvant that enhances the immunogenicity of certain vaccines in experimental animal models. In this study, three recombinant proteins: PCV2-Cap protein, porcine IFN-γ (PoIFN-γ), and the fusion protein (Cap-PoIFN-γ) of PCV2-Cap protein and PoIFN-γ were respectively expressed in the baculovirus system, and analyzed by Western blot and indirect ELISA. Additionally, we evaluated the enhancement of the protective immune response to the Cap protein-based PCV2 subunit vaccine elicited by co-administration of PoIFN-γ in mice. Vaccination of mice with the PCV2-Cap+PoIFN-γ vaccine elicited significantly higher levels of PCV2-specific IPMA antibodies, neutralizing antibodies, and lymphocyte proliferative responses compared to the Cap-PoIFN-γ vaccine, the PCV2-Cap vaccine, and LG-strain. Following virulent PCV2 challenge, no viraemia was detected in all immunized groups, and the viral loads in lungs of the PCV2-Cap+PoIFN-γ group were significantly lower compared to the Cap-PoIFN-γ group, the LG-strain group, and the mock group, but slightly lower compared to the PCV2-Cap group. These findings suggested that PoIFN-γ substantially enhanced the protective immune response to the Cap protein-based PCV2 subunit vaccine, and that the PCV2-Cap+PoIFN-γ subunit vaccine potentially serves as an attractive candidate vaccine for the prevention and control of PCV2-associated diseases.

[Establishment of cell lines derived from skin biopsies of crested ibis (Nipponia nippon) and their biological characteristics].

The crested ibis is among the rarest and most endangered species worldwide. To preserve its genetic resources and conveniently provide materials for biological research, we successfully established two cell lines from biopsies of a male and female adult crested ibis. The cultured cells from both specimens had typical fibroblast morphology. Immunofluorescence staining revealed that the cultured cells strongly expressed the marker of smooth muscle specific α-actin, clearly indicating the cells were from the smooth muscle tissue. Growth property analysis showed that the cells grew well past the first 10 passages and continued growing with reduced proliferation after 15 passages, but ceased by passage 25 as the cells could not grow to form a confluent monolayer. From these two cell lines, we harvested mitotic metaphase chromosomes and conducted different staining, banding, and fluorescent in situ hybridization. Throughout the process, cells maintained normal diploidy, with the karyotypes of these two cell lines being 2n=68, ZZ in the male and 2n=68, ZW in the female. Patterns of Ag staining, C- and G-bands of the crested ibis chromosomes were also studied. Banding analyses and fluorescent in situ hybridization also allowed identification of the sex chromosomes. We suggest that the external implants method for establishing primary cell lines used in this study may also be applicable to other birds, especially similarly endangered avian species.

The dopamine D1 but not D3 receptor plays a fundamental role in spatial working memory and BDNF expression in prefrontal cortex of mice.

Although dopamine within the prefrontal cortex has been implicated in working memory, how different dopamine receptor subtypes contribute to this process need to be further characterized. Previous studies have suggest the importance of dopamine receptors signaling in regulating the brain-derived neurotrophic factor (BDNF) function that is associated with synaptic plasticity underlying normal memory formation. Changes in BDNF expression through the dopamine receptors within the prefrontal cortex may accompany and mediate the spatial working memory. To test the possibility, dopamine D1 and D3 receptor mutant mice were tested in Morris water maze for spatial working memory. We found that trial-dependent, matching-to-sample, learning of the platform location, an index of short-term spatial working memory in mice, was significantly impaired in D1 receptor knockout mice compared to wild-type mice, and regular performance of D3 receptor mutants was observed in the similar working memory task. BDNF protein was significantly decreased in prefrontal cortex, though not in hippocampus, of the D1 receptor knockout mice, whereas no changes were found in both prefrontal cortex and hippocampus of D3 receptor knockout mice. These data suggest that dopamine D1 but not D3 receptors are critical for prefrontal cortex BDNF expression which may be related to spatial working memory processes.

Long-term in vitro treatment of INS-1 rat pancreatic ß-cells by unsaturated free fatty acids protects cells against gluco- and lipotoxicities via activation of GPR40 receptors.

G-protein coupled receptor 40 (GPR40) is a membrane-bound G-protein-coupled receptor with high binding affinity to medium- and long-chain free fatty acids (FFAs). Acute activation of GPR40 on pancreatic ß-cells causes insulin secretion, whereas prolonged activation may contribute to a deterioration of the effect of saturated FFAs on ß-cells. It has been documented that different types of FFAs produce various effects on insulin secretion; however, little information is available regarding the expression of GPR40 and its function after long-term exposure of ß-cells to unsaturated FFAs. In the present study, GPR40 expression and function were assessed in INS-1 ß-cells after 48 h exposure to different types of unsaturated FFAs. The mRNA and protein expression of GPR40 was increased significantly by long-term exposure of cells to polyunsaturated α-linolenic acid, but not to either oleic acid or linoleic acid. Immunocytochemistry revealed a reduction in the number of insulin-containing granules in cells treated with α-linolenic acid, which was correlated with an increase in cellular expression of GPR40. Basal and glucose-stimulated insulin secretion were markedly suppressed by 48 h treatment of cells with saturated palmitic acid, but not unsaturated α-linolenic acid. By testing various FFAs, it was found that FFA-induced suppression of basal and glucose-stimulated insulin secretion was attenuated by an increase in the degree of unsaturation of the FFAs and GPR40 expression in response to FFA treatment in INS-1 cells. The results of the present study indicate that long-term in vitro treatment of INS-1 rat pancreatic ß-cells by unsaturated FFAs protects the cells against from gluco- and lipotoxicities and that this coincides with an increase in GPR40 expression.

Association study of monoamine oxidase A/B genes and schizophrenia in Han Chinese.

BACKGROUND: Monoamine oxidases (MAOs) catalyze the metabolism of dopaminergic neurotransmitters. Polymorphisms of isoforms MAOA and MAOB have been implicated in the etiology of mental disorders such as schizophrenia. Association studies detected these polymorphisms in several populations, however the data have not been conclusive to date. Here, we investigated the association of MAOA and MAOB polymorphisms with schizophrenia in a Han Chinese population. METHODS: Two functional single nucleotide polymorphisms (SNPs), rs6323 of MAOA and rs1799836 of MAOB, were selected for association analysis in 537 unrelated schizophrenia patients and 536 healthy controls. Single-locus and Haplotype associations were calculated. RESULTS: No differences were found in the allelic distribution of rs6323. The G allele of rs1799836 was identified as a risk factor in the development of schizophrenia (P = 0.00001). The risk haplotype rs6323T-rs1799836G was associated with schizophrenia in female patients (P = 0.0002), but the frequency difference was not significant among male groups. CONCLUSIONS: Our results suggest that MAOB is a susceptibility gene for schizophrenia. In contrast, no significant associations were observed for the MAOA functional polymorphism with schizophrenia in Han Chinese. These data support further investigation of the role of MAO genes in schizophrenia.

An association study between dopamine D1 receptor gene polymorphisms and the risk of schizophrenia.

Deficits in dopamine transmission at D1 receptors in the PFC are implicated in schizophrenia. Genetic polymorphisms in functional regions of DRD1 have a plausible role in modulating the risk of schizophrenia. In order to evaluate the role of DRD1 polymorphisms as a risk factor for schizophrenia, we performed a detailed analysis of possible functional single nucleotide polymorphisms (SNPs) in regulatory and coding regions of DRD1. Nine SNPs were identified by DNA sequencing in 20 patients with schizophrenia. Then 385 cases and 350 healthy control subjects were genotyped using the nine SNPs (rs4867798, rs686, rs1799914, rs4532 rs5326, rs265981, rs10078714, rs10063995, rs10078866). Statistically significant differences were observed in the allelic or genotypic frequencies of the rs686 and rs10063995 polymorphism in the DRD1 gene. A significantly lower risk of schizophrenia was associated with the G allele and AG+GG genotype of rs686 (OR (G allele)=0.632, 95%CI (G allele): 0.470-0.849; OR (AG+GG genotype)=0.578, 95%CI (AG+GG genotype): 0.416-0.803) compared with the A allele and AA genotype, respectively. And a significantly increased risk of schizophrenia was associated with the T allele of rs10063995 (OR=1.446, 95%CI: 1.125-1.859) compared with the G allele. The haplotype analysis indicated the G-T variant containing the T allele of rs10063995 is a risk for schizophrenia (P=0.005, OR=1.467, 95%CI: 1.123-1.917). These data suggest that DRD1 gene polymorphisms confer susceptibility to schizophrenia, and also support the notion that dysfunction of DRD1 is involved in the pathophysiological process of schizophrenia.

Effects of pre-training morphine on spatial memory acquisition and retrieval in mice.

The opioid system plays an important role in memory processess. Morphine mimics endogenous opioids by acting on opioid receptor in brain to regulate memory. However, the effects of morphine on spatial memory acquisition are controversial. Also, little evidence has suggested that morphine could affect the retrieval of spatial memory. In the current study, effects of pre-training morphine and naloxone on the acquisition vs. retrieval of spatial reference vs. working memory were examined using discrete water maze tasks in C57BL/6 mice. Pre-training morphine administration (7.5 and 15 mg/kg, i.p.) impaired the acquisition of both spatial reference memory and working memory. Motivation to escape from the water maze was not affected by morphine. Pre-test morphine also inhibited the retrieval of spatial working memory but not reference memory. The effects of morphine on the acquisition and retrieval of spatial working memory were eliminated by naloxone pretreatment (1mg/kg). These results indicate that morphine could differentially modulate a variety of aspects of spatial memory and these effects are mediated by the mu-opioid receptor.

[Genetic differentiation and patterns of gene flow of ten minorities in Yunnan province].

OBJECTIVE: To explore the features of genetic differentiation and gene flow of ten minorities in Yunnan province according to nine CODIS short tandem repeat(STR) loci (CSF1PO, FGA, THO1, TPOX, v WA, D3S1358, D5S818, D7S820 and D13S317). METHODS: Heterozygosity and parameters of population differentiation such as F, theta, f and Gst at each locus were calculated. DA genetic distance and fixation index Fst were calculated by Phylip 3.6 and Arlequin 3.0 software, respectively. Phylogenetic trees were constructed by Mega 3.0, and the patterns of gene flow were analyzed by R-matrix model. RESULTS: It showed that average genetic heterogeneity in ten minorities was above 0.7. Significant difference was found for most of the loci in genetic differentiation. Phylogenetic tree analysis showed that the ten minorities were divided into two clusters. The results of the R-matrix analysis showed that the gene flow of Yi and Dai minorities were higher than that of other minorities, while the pattern of gene flow of Dulong minority demonstrated some of the isolation. CONCLUSION: Nine STR loci commonly used in forensic identification show a high polymorphism. Heterozygosity can be used for investigating genetic differentiation and gene flow of minority. The ten minorities in Yunnan are independent populations, while the level of differentiation is not high. The relationship in evolution is not far from each other and shows a widely gene flow among the minorities.

[Polymorphism of fifteen short tandem repeat loci in Tibetan of Changdu area].

OBJECTIVE: To investigate the genetic polymorphism of 15 autosomal short tandem repeat (STR) loci, i.e. D5S818, FGA, D8S1179, D21S11, D7S820, CSF1PO, D3S1358, TH01, D13S317, D16S539, D2S1338, D19S433, vWA, TPOX and D18S51, in Tibetan population of Changdu area, and to analyze the genetic relationship between this population and other Asian populations. METHODS: The 15 loci were amplified simultaneously using a multiplex PCR typing system. Amplified STR fragments were analyzed with an ABI PRISM 3100 Avant DNA Analyzer. Arlequin software version 3.1 was used to obtain allele frequencies and polymorphism parameters. RESULTS: There were 135 STR alleles in the 15 STRs of Changdu Tibetan, with allele frequencies ranging from 0.0065 to 0.5455. The average heterozygosity was 0.7340, the discrimination power was higher than 0.8 except for TPOX and TH01. The accumulative discrimination power was more than 0.9999998, and the accumulative non-parental exclusion probability was 0.99999997. CONCLUSION: The 15 STR loci of Changdu Tibetan possess characteristics of high genetic diversity. They can be employed in minority genetics investigation, and individual and paternity test in forensic medicine.

Potential association of DRD2 and DAT1 genetic variation with heroin dependence.

The aim of our study was to investigate the potential association of dopamine receptor D2 gene (DRD2) TaqI RFLP A (rs1800497) and dopamine transporter gene (DAT) 3'untranslated region VNTR genetic variations with heroin addiction. Genotyping was performed using PCR-based techniques in 530 heroin abusers and 500 controls. Our results showed that DRD2 TaqI A1 allele carriers (genotypes A1A1 and A1A2) were prone to heroin abuse in models of dominance or co-dominance. We detected a 12 repeat allele and 6/6, 7/9, 9/11, 10/12 genotype in a Chinese/eastern Asian population for the first time. However, no significant differences in the DAT1 VNTR were found between the two groups in either genotypic or allelic distributions and there was no gene interaction between the two genetic loci.

[Genetic polymorphisms of X-STR loci in Chinese Yugur ethnic group and its application].

To study the genetic polymorphism of nine short tandem repeats (STRs) loci (DXS7130, DXS7132, DXS6804, DXS7423, DXS7424, DXS6789, DXS6799, DXS8378, and HPRTB) on X chromosome in Chinese Yugur ethnic group. The allele and genotype frequency of nine X-STR loci among 120 unrelated individuals (55 female, 65 male) from Yugur ethnic group were analyzed using PCR and followed by polyacrylamide gel electrophoresis and silver staining. The numbers of alleles in the nine X-STR loci were 8, 6, 6, 5, 6, 7, 6, 4, and 6, respectively; the numbers of genotypes in the nine loci were 16, 14, 13, 6, 13, 20, 11, 6, and 12, respectively. The genotype frequencies in females were in accordance with Hardy-Weinberg equilibrium (P>0.05). The nine X-STR loci were relatively abundant in polymorphic information for individual identification, paternity testing and population genetics. A total of 15 haplotypes were detected in DXS7130 and DXS8378 loci, and 55 haplotypes were detected in DXS6789, DXS6799, DXS7424, and DXS6804 loci. The haplotype diversity reached 0.8212 and 0.9947, respectively. Phylogeny tree and cluster analysis based on X-STR allele frequencies in genesis showed that Yugur ethnic group share a close relationship with Mongolian ethnic group and Chinese Han, Tibetan population and far from Hui and Uygur ethnic group, who dwell in the northwest of China.

[The role of epigenetic regulation in etiology of major depressive disorder].

Epigenetics refers to the heritable, but reversible, regulation of various biological functions mediated principally through changes in DNA methylation and chromatin structure derived from histone modification. Recent research indicated that epigenetic mechanisms may play vital role in etiology of major psychosis, such as schizophrenia, bipolar disorder and drug addiction. With brief introduction of epigenetic molecular mechanisms and relevance of epigenetics to human common diseases, this review focuses on epigenetic hypothesis and some supporting evidence which are recently emerged in major depressive disorder (MDD).