RESUMO
OBJECTIVE: The main aim of the current study was to investigate whether the expression levels of the HTR2A and MAOA genes are altered in the postmortem brain of suicide victims from Mexican population. METHODS: On the basis of a case- control study, we examined the expression levels of HTR2A and MAOA genes in the postmortem prefrontal cortex (Brodmann area 8/9) and hypothalamus (ventromedial nucleus) tissues from 20 suicide victims and 20 control subjects from a Mexican population. Gene-expression profile quantification was carried out by qPCR and determined by the 2-ΔΔCt method. RESULTS: In suicide victims, the expression levels of the HTR2A gene were significantly higher in the prefrontal cortex. In contrast, the expression of the MAOA gene in the hypothalamus of the suicide victims was significantly higher than in the control subjects. These results were consistent regardless of age, sex, postmortem interval, or pH of brain tissue. CONCLUSION: The evidence suggests that the pattern of differential expression of HTR2A and MAOA genes in the brain may be involved in suicide, providing a possible molecular basis for the brain abnormalities in suicide victims.
Assuntos
Suicídio , Encéfalo/metabolismo , Estudos de Casos e Controles , Humanos , Hipotálamo , Córtex Pré-Frontal/metabolismoRESUMO
BACKGROUND: Obsessive-compulsive disorder (OCD) is characterized by intrusive thoughts and repetitive actions, that presents the involvement of the cortico-striatal areas. The contribution of environmental risk factors to OCD development suggests that epigenetic mechanisms may contribute to its pathophysiology. DNA methylation changes and gene expression were evaluated in post-mortem brain tissues of the cortical (anterior cingulate gyrus and orbitofrontal cortex) and ventral striatum (nucleus accumbens, caudate nucleus and putamen) areas from eight OCD patients and eight matched controls. RESULTS: There were no differentially methylated CpG (cytosine-phosphate-guanine) sites (DMSs) in any brain area, nevertheless gene modules generated from CpG sites and protein-protein-interaction (PPI) showed enriched gene modules for all brain areas between OCD cases and controls. All brain areas but nucleus accumbens presented a predominantly hypomethylation pattern for the differentially methylated regions (DMRs). Although there were common transcriptional factors that targeted these DMRs, their targeted differentially expressed genes were different among all brain areas. The protein-protein interaction network based on methylation and gene expression data reported that all brain areas were enriched for G-protein signaling pathway, immune response, apoptosis and synapse biological processes but each brain area also presented enrichment of specific signaling pathways. Finally, OCD patients and controls did not present significant DNA methylation age differences. CONCLUSIONS: DNA methylation changes in brain areas involved with OCD, especially those involved with genes related to synaptic plasticity and the immune system could mediate the action of genetic and environmental factors associated with OCD.
Assuntos
Encéfalo/metabolismo , Metilação de DNA , Transtorno Obsessivo-Compulsivo/genética , Idoso , Núcleo Caudado , Ilhas de CpG/genética , Feminino , Giro do Cíngulo , Humanos , Sistema Imunitário/metabolismo , Imunidade/genética , Masculino , Plasticidade Neuronal/genética , Núcleo Accumbens , Córtex Pré-Frontal , PutamenAssuntos
MicroRNAs/biossíntese , Infecção por Zika virus/congênito , Infecção por Zika virus/metabolismo , Encéfalo/metabolismo , Encéfalo/virologia , Linhagem Celular Tumoral , Feminino , Regulação da Expressão Gênica/genética , Humanos , Recém-Nascido , Microcefalia/genética , Microcefalia/virologia , Neurônios/metabolismo , Neurônios/virologia , Gravidez , Complicações Infecciosas na Gravidez/metabolismo , Complicações Infecciosas na Gravidez/virologia , Natimorto , Regulação para CimaRESUMO
Here we describe a mass spectrometry-based proteomics workflow to discovery proteins differentially regulated in brains collected postmortem from mental, neurological, or substance abuse disorders (MNS) patients. One way to maximize protein detection is to carry out enrichment of cellular compartments such as the nucleus, mitochondria and cytosol. Subcellular fractionation improves proteome coverage and may shed light on the role of these organelles in the pathophysiology of MNS.
Assuntos
Encefalopatias/genética , Cromatografia Líquida/métodos , Espectrometria de Massas/métodos , Proteômica/métodos , Encefalopatias/patologia , Núcleo Celular/genética , Núcleo Celular/patologia , Humanos , Proteoma/genética , Frações Subcelulares/patologiaRESUMO
Approximately 25 % of the world population is affected by a mental disorder at some point in their life. Yet, only in the mid-twentieth century a biological cause has been proposed for these diseases. Since then, several studies have been conducted toward a better comprehension of those disorders, and although a strong genetic influence was revealed, the role of these genes in disease mechanism is still unclear. This led most recent studies to focus on the molecular basis of mental disorders. One line of investigation that has risen in the post-genomic era is proteomics, due to its power of revealing proteins and biochemical pathways associated with biological systems. Therefore, this review compiled and analyzed data of differentially expressed proteins, which were found in postmortem brain studies of the three most prevalent psychiatric diseases: schizophrenia, bipolar disorder and major depressive disorders. Overviewing both the proteomic methods used in postmortem brain studies, the most consistent metabolic pathways found altered in these diseases. We have unraveled those disorders share about 21 % of proteins affected, and though most are related to energy metabolism pathways deregulation, the main differences found are 14-3-3-mediated signaling in schizophrenia, mitochondrial dysfunction in bipolar disorder and oxidative phosphorylation in depression.
Assuntos
Encéfalo/metabolismo , Transtornos Mentais/metabolismo , Transtornos Mentais/patologia , Proteômica , Transdução de Sinais/fisiologia , HumanosRESUMO
Schizophrenia is an incurable and debilitating mental disorder that may affect up to 1% of the world population. Morphological, electrophysiological, and neurophysiological studies suggest that the corpus callosum (CC), which is the largest portion of white matter in the human brain and responsible for inter-hemispheric communication, is altered in schizophrenia patients. Here, we employed mass spectrometry-based proteomics to investigate the molecular underpinnings of schizophrenia. Brain tissue samples were collected postmortem from nine schizophrenia patients and seven controls at the University of Heidelberg, Germany. Because the CC has a signaling role, we collected cytoplasmic (soluble) proteins and submitted them to nano-liquid chromatography-mass spectrometry (nano LC-MS/MS). Proteomes were quantified by label-free spectral counting. We identified 5678 unique peptides that corresponded to 1636 proteins belonging to 1512 protein families. Of those proteins, 65 differed significantly in expression: 28 were upregulated and 37 downregulated. Our data increased significantly the knowledge derived from an earlier proteomic study of the CC. Among the differentially expressed proteins are those associated with cell growth and maintenance, such as neurofilaments and tubulins; cell communication and signaling, such as 14-3-3 proteins; and oligodendrocyte function, such as myelin basic protein and myelin-oligodendrocyte glycoprotein. Additionally, 30 of the differentially expressed proteins were found previously in other proteomic studies in postmortem brains; this overlap in findings validates the present study and indicates that these proteins may be markers consistently associated with schizophrenia. Our findings increase the understanding of schizophrenia pathophysiology and may serve as a foundation for further treatment strategies.