GISELE RODRIGUES GOUVEIA
Projetos de Pesquisa
Unidades Organizacionais
Departamento de Psiquiatria, Faculdade de Medicina
LIM/21 - Laboratório de Neuroimagem em Psiquiatria, Hospital das Clínicas, Faculdade de Medicina
LIM/21 - Laboratório de Neuroimagem em Psiquiatria, Hospital das Clínicas, Faculdade de Medicina
10 resultados
Resultados de Busca
Agora exibindo 1 - 10 de 10
- Initial findings of striatum tripartite model in OCD brain samples based on transcriptome analysis(2019) LISBOA, Bianca C. G.; OLIVEIRA, Katia C.; TAHIRA, Ana Carolina; BARBOSA, Andre Rocha; FELTRIN, Arthur Sant'Anna; GOUVEIA, Gisele; LIMA, Luzia; SANTOS, Ana Cecilia Feio dos; JR, David Correa Martins; PUGA, Renato David; MORETTO, Ariane Cristine; PEREIRA, Carlos Alberto De Braganca; LAFER, Beny; LEITE, Renata Elaine Paraizo; FERRETTI-REBUSTINI, Renata Eloah De Lucena; FARFEL, Jose Marcelo; GRINBERG, Lea Tenenholz; JACOB-FILHO, Wilson; MIGUEL, Euripedes Constantino; HOEXTER, Marcelo Queiroz; BRENTANI, HelenaObsessive-compulsive disorder (OCD) is a psychiatric disorder characterized by obsessions and/or compulsions. Different striatal subregions belonging to the cortico-striato-thalamic circuitry (CSTC) play an important role in the pathophysiology of OCD. The transcriptomes of 3 separate striatal areas (putamen (PT), caudate nucleus (CN) and accumbens nucleus (NAC)) from postmortem brain tissue were compared between 6 OCD and 8 control cases. In addition to network connectivity deregulation, different biological processes are specific to each striatum region according to the tripartite model of the striatum and contribute in various ways to OCD pathophysiology. Specifically, regulation of neurotransmitter levels and presynaptic processes involved in chemical synaptic transmission were shared between NAC and PT. The Gene Ontology terms cellular response to chemical stimulus, response to external stimulus, response to organic substance, regulation of synaptic plasticity, and modulation of synaptic transmission were shared between CN and PT. Most genes harboring common and/or rare variants previously associated with OCD that were differentially expressed or part of a least preserved coexpression module in our study also suggest striatum subregion specificity. At the transcriptional level, our study supports differences in the 3 circuit CSTC model associated with OCD.
- An integrative approach to investigate the respective roles of single-nucleotide variants and copy-number variants in Attention-Deficit/Hyperactivity Disorder(2016) LIMA, Leandro de Araujo; FEIO-DOS-SANTOS, Ana Cecilia; BELANGERO, Sintia Iole; GADELHA, Ary; BRESSAN, Rodrigo Affonseca; SALUM, Giovanni Abrahao; PAN, Pedro Mario; MORIYAMA, Tais Silveira; GRAEFF-MARTINS, Ana Soledade; TAMANAHA, Ana Carina; ALVARENGA, Pedro; KRIEGER, Fernanda Valle; FLEITLICH-BILYK, Bacy; JACKOWSKI, Andrea Parolin; BRIETZKE, Elisa; SATO, Joao Ricardo; POLANCZYK, Guilherme Vanoni; MARI, Jair de Jesus; MANFRO, Gisele Gus; ROSARIO, Maria Conceicao do; MIGUEL, Euripedes Constantino; PUGA, Renato David; TAHIRA, Ana Carolina; SOUZA, Viviane Neri; CHILE, Thais; GOUVEIA, Gisele Rodrigues; SIMOES, Sergio Nery; CHANG, Xiao; PELLEGRINO, Renata; TIAN, Lifeng; GLESSNER, Joseph T.; HASHIMOTO, Ronaldo Fumio; ROHDE, Luis Augusto; SLEIMAN, Patrick M. A.; HAKONARSON, Hakon; BRENTANI, HelenaMany studies have attempted to investigate the genetic susceptibility of Attention-Deficit/Hyperactivity Disorder (ADHD), but without much success. The present study aimed to analyze both single-nucleotide and copy-number variants contributing to the genetic architecture of ADHD. We generated exome data from 30 Brazilian trios with sporadic ADHD. We also analyzed a Brazilian sample of 503 children/adolescent controls from a High Risk Cohort Study for the Development of Childhood Psychiatric Disorders, and also previously published results of five CNV studies and one GWAS meta-analysis of ADHD involving children/adolescents. The results from the Brazilian trios showed that cases with de novo SNVs tend not to have de novo CNVs and vice-versa. Although the sample size is small, we could also see that various comorbidities are more frequent in cases with only inherited variants. Moreover, using only genes expressed in brain, we constructed two ""in silico"" protein-protein interaction networks, one with genes from any analysis, and other with genes with hits in two analyses. Topological and functional analyses of genes in this network uncovered genes related to synapse, cell adhesion, glutamatergic and serotoninergic pathways, both confirming findings of previous studies and capturing new genes and genetic variants in these pathways.
- Molecular characterization of viruses associated with encephalitis in Sao Paulo, Brazil(2019) FERREIRA, Jerenice E.; FERREIRA, Suzete C.; ALMEIDA-NETO, Cesar; NISHIYA, Anna S.; ALENCAR, Cecilia S.; GOUVEIA, Gisele R.; CAIAFFA-FILHO, Helio; GOMES, Helio; SANTOSID, Raimunda Telma de Macedo; WITKIN, Steven S.; MENDRONE-JUNIOR, Alfredo; SABINO, Ester C.The objective of this study was to characterize the prevalence of viral encephalitis due to arbovirus infection of the Togaviridae and Flaviviridae families in Sao Paulo, Brazil. A total of 500 cerebrospinal fluid (CSF) samples collected between August 2012 and January 2013, from patients with symptoms of acute encephalitis were analyzed. Findings suggestive of viral encephalitis-elevations in cell concentration, glucose and total protein-were observed in 234 (46.8%) samples, designated as Group 1. The remaining 266 samples comprised Group 2. All samples were tested for Flaviviruses (dengue virus 1, 2, 3 and 4, yellow fever virus and West Nile virus), Alphavirus (NS5 region) and enterovirus by RT-PCR and for herpesviruses and enteroviruses using CLART(-)Entherpex. A presumptive viral etiological agent was detected in 26 samples (5.2%), 18 (8.0%) in Group 1 and 8 (3.0%) in Group 2. In Group 1 human herpesviruses were detected in 9 cases, enteroviruses in 7 cases, dengue viruses (DENV) in 2 CSFs and St. Louis encephalitis virus (SLEV) in one case. In Group 2 there were 3 CSFs positive for human herpesviruses, 2 for enteroviruses, 2 for DENV and 1 for SLEV. Detection of arboviruses, even though present in a minority of infected patients, identifies these viruses as a probable etiological agent of encephalitis. This is of special concern in regions where this class of viruses is endemic and has been linked to other recent epidemics.
- Genome-wide DNA methylation profile in the peripheral blood of cocaine and crack dependents(2019) CAMILO, Caroline; MASCHIETTO, Mariana; VIEIRA, Henrique C.; TAHIRA, Ana C.; GOUVEIA, Gisele R.; SANTOS, Ana C. Feio dos; NEGRAO, Andre B.; RIBEIRO, Marcelo; LARANJEIRA, Ronaldo; VALLADA, Homero; BRENTANI, HelenaObjective: Cocaine use disorders (CUDs) represent a major public health problem in many countries. To better understand the interaction between the environmental modulations and phenotype, the aim of the present study was to investigate the DNA methylation pattern of CUD patients, who had concomitant cocaine and crack dependence, and healthy controls. Methods: We studied DNA methylation profiles in the peripheral blood of 23 CUD patients and 24 healthy control subjects using the Illumina Infinium HumanMethylation450 BeadChip arrays. Results: Comparison between CUD patients and controls revealed 186 differentially methylated positions (DMPs; adjusted p-value [adjP] < 10(-5)) related to 152 genes, with a subset of CpGs confirmed by pyrosequencing. DNA methylation patterns discriminated CUD patients and control groups. A gene network approach showed that the EHMT1, EHMT2, MAPK1, MAPK3, MAP2K1, and HDAC5 genes, which are involved in transcription and chromatin regulation cellular signaling pathways, were also associated with cocaine dependence. Conclusion: The investigation of DNA methylation patterns may contribute to a better understanding of the biological mechanisms involved in CUD.
- Overexpression of OCT-1 gene is a biomarker of adverse prognosis for diffuse large B-cell lymphoma (DLBCL): data from a retrospective cohort of 77 Brazilian patients(2020) GOUVEIA, Gisele R.; FERREIRA, Suzete C.; SIQUEIRA, Sheila A. C.; LAGE, Luis Alberto de Padua Covas; HALLACK NETO, Abrahao E.; COSTA, Renata de Oliveira; PEREIRA, JulianaBackgroundOCT-1 gene is a member of the POU-homeodomain family of transcriptional regulators of B-lymphocyte differentiation by controlling expression of B-cell specific genes. BCL-2 gene is a potent inhibitor of apoptosis and it is essential during B-cell differentiation into germinal center. These genes may be expressed in diffuse large B-cell lymphoma (DLBCL), but the role of BCL-2 in its prognosis has been contradictory, and OCT-1 has yet to be tested.MethodsIn this study, we aimed to investigate the prognostic impact of OCT-1 and BCL-2 expression in DLBCL treated in the real world with immunochemotherapy in a single center. BCL-2 and OCT-1 genes were available in 78.5% (77/98) DLBCL patients, and the RNA for quantitative real-time PCR was isolated from formalin-fixed paraffin-embedded samples. The values obtained for gene expression were transformed in categorical variable according to their median.ResultsCohort median age was 54.5years (15-84), 49 (50%) were male, 38/77 (49.4%) and 40/77 (51.9%) presented OCT-1 and BCL-2 expression >= median, respectively. The overall response rate (ORR) in all patients was 68.4% (67/98), 65,3% (64/98) of patients acquired complete response, and 3.1% (3/98) partial response, while 6.1% (6/98) were primary refractory. The median follow-up was 3.77years (95% CI: 3.2-4.1), with 5.43 (95% CI: 2.2-NR) of overall survival (OS) and 5.15years (95% CI: 2.9-NA) of progression free survival (PFS). OCT-1 >= median was associated with shorter OS at univariate analysis (p =0.013; [HR] 2.450, 95% CI: 1.21-4.96) and PFS (p =0.019; [HR] 2.270, 95%CI: 1.14-4.51) and BCL-2 gene overexpression presented worse PFS (p =0.043, [HR] 2.008, 95% CI: 1.02-3.95). At multivariate analysis, OCT-1 overexpression was associated with poor PFS (p =0.035, [HR] 2.22, 95% CI: 1.06-4.67).ConclusionIn this study, we showed that overexpression of OCT1 gene was an independent prognostic factor of adverse outcomes in DLBCL.
- Gestational age acceleration is associated with epigenetic biomarkers of prenatal physiologic stress exposure(2022) EUCLYDES, Veronica; GOMES, Catarina; GOUVEIA, Gisele; GASTALDI, Vinicius Daguano; FELTRIN, Arthur Sant'Anna; CAMILO, Caroline; VIEIRA, Rossana Pulcineli; FELIPE-SILVA, Aloisio; GRISI, Sandra; FINK, Gunther; BRENTANI, Alexandra; BRENTANI, HelenaBackground Physiological maternal stress response, such as imbalance in the glucocorticoid pathway and immune system seems to be mediated by DNA methylation (DNAm) and might translate intrauterine stress exposures into phenotypic changes in a sex-specific manner. DNAm in specific sites can also predict newborn gestational age and gestational age acceleration (GAA). GAA occurs when the predicted biological age is higher than the chronological age. In adults, poor health outcomes related to this deviance are well documented and raise questions for the interpretation and prediction in early stages of life. Boys seem to be more vulnerable to intrauterine stress exposure than girls; however, the mechanisms of adaptive sex-specific responses are still unclear. We hypothesize that intrauterine stress exposure is associated with GAA and could be different in boys and girls if inflammatory or glucocorticoid pathways exposure is considered. Results Using the Western Region Birth Cohort (ROC-Sao Paulo, Brazil) (n = 83), we calculated DNAm age and GAA from cord blood samples. Two epigenetic risk scores were calculated as an indirect proxy for low-grade inflammation (i-ePGS) and for glucocorticoid exposure (GES). Multivariate linear regression models were applied to investigate associations of GAA with prenatal exposures. The i-ePGS and GES were included in different models with the same co-variates considering sex interactions. The first multivariate model investigating inflammatory exposure (adj. R-2 = 0.31, p = < 0.001) showed that GAA was positively associated with i-ePGS (CI, 0.26-113.87, p = 0.049) and negative pregnancy-related feelings (CI, 0.04-0.48 p = 0.019). No sex interaction was observed. The second model investigating glucocorticoid exposure (adj. R-2 = 0.32, p = < 0.001) showed that the higher was the GAA was associated with a lower the lower was the GES in girls (CI, 0.04-2.55, p = 0.044). In both models, maternal self-reported mental disorder was negatively associated with GAA. Conclusion Prenatal epigenetic score of exposure to low-grade inflammatory was a predictor of GAA for both sexes. Glucocorticoid epigenetic score seems to be more important to GAA in girls. This study supports the evidence of sex-specificity in stress response, suggesting the glucocorticoid as a possible pathway adopted by girls to accelerate the maturation in an adverse condition.
- Pathophysiology and molecular aspects of diffuse large B-cell lymphoma(2012) GOUVEIA, Gisele Rodrigues; SIQUEIRA, Sheila Aparecida Coelho; PEREIRA, JulianaDiffuse large B-Cell lymphoma is the most common subtype of non-Hodgkin lymphoma in the West. In Brazil, it is the fifth cause of cancer, with more than 55,000 cases and 26,000 deaths per year. At Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo - HCFMUSP, diffuse large B-Cell lymphoma represents 49.7% of all non-Hodgkin lymphoma cases. Initially, the classification of non-Hodgkin lymphoma was based on morphology, but advances in immunology and molecular medicine allowed the introduction of a biological classification for these diseases. As for other cancers, non-Hodgkin lymphoma involves patterns of multi factorial pathogenesis with environmental factors, as well as genetic, occupational and dietary factors, contributing to its development. Multiple lesions involving molecular pathways of B-cell proliferation and differentiation may result in the activation of oncogenes such as the BCL2, BCL6,and MYC genes and the inactivation of tumor suppressor genes such as p53 and INK4, as well as other important transcription factors such as OCT-1 and OCT-2. A dramatic improvement in survival was seen after the recent introduction of the anti-CD20 monoclonal antibody. The association of this antibody to the cyclophosphamide, hydroxydaunorubicin, oncovin and prednisolone (CHOP) regimen has increased overall survival of diffuse large B-Cell lymphoma and follicular lymphoma patients by 20%. However, 50% of all diffuse large B-Cell lymphoma patients remain incurable, creating a demand for more research with new advances in treatment. Thus, it is important to know and understand the key factors and molecular pathways involved in the pathogenesis of diffuse large B-Cell lymphoma.
- An integrative approach to investigate the respective roles of single-nucleotide variants and copy-number variants in Attention-Deficit/Hyperactivity Disorder (vol 6, 22851, 2016)(2016) LIMA, Leandro de Araujo; FEIO-DOS-SANTOS, Ana Cecilia; BELANGERO, Sintia Iole; GADELHA, Ary; BRESSAN, Rodrigo Affonseca; SALUM, Giovanni Abrahao; PAN, Pedro Mario; MORIYAMA, Tais Silveira; GRAEFF-MARTINS, Ana Soledade; TAMANAHA, Ana Carina; ALVARENGA, Pedro; KRIEGER, Fernanda Valle; FLEITLICH-BILYK, Bacy; JACKOWSKI, Andrea Parolin; BRIETZKE, Elisa; SATO, Joao Ricardo; POLANCZYK, Guilherme Vanoni; MARI, Jair de Jesus; MANFRO, Gisele Gus; ROSARIO, Maria Conceiao do; MIGUEL, Euripedes Constantino; PUGA, Renato David; TAHIRA, Ana Carolina; SOUZA, Viviane Neri; CHILE, Thais; GOUVEIA, Gisele Rodrigues; SIMOES, Sergio Nery; CHANG, Xiao; PELLEGRINO, Renata; TIAN, Lifeng; GLESSNER, Joseph T.; HASHIMOTO, Ronaldo Fumio; ROHDE, Luis Augusto; SLEIMAN, Patrick M. A.; HAKONARSON, Hakon; BRENTANI, Helena
- Sex differences in DNA methylation of the cord blood are related to sex-bias psychiatric diseases(2017) MASCHIETTO, Mariana; BASTOS, Laura Caroline; TAHIRA, Ana Carolina; BASTOS, Elen Pereira; EUCLYDES, Veronica Luiza Vale; BRENTANI, Alexandra; FINK, Gunther; BAUMONT, Angelica de; FELIPE-SILVA, Alosio; FRANCISCO, Rossana Pulcineli Vieira; GOUVEIA, Gisele; GRISI, Sandra Josefina Ferraz Ellero; ESCOBAR, Ana Maria Ulhoa; MOREIRA-FILHO, Carlos Alberto; POLANCZYK, Guilherme Vanoni; MIGUEL, Euripedes Constantino; BRENTANI, HelenaSex differences in the prevalence of psychiatric disorders are well documented, with exposure to stress during gestation differentially impacting females and males. We explored sex-specific DNA methylation in the cord blood of 39 females and 32 males born at term and with appropriate weight at birth regarding their potential connection to psychiatric outcomes. Mothers were interviewed to gather information about environmental factors (gestational exposure) that could interfere with the methylation profiles in the newborns. Bisulphite converted DNA was hybridized to Illumina HumanMethylation450 BeadChips. Excluding XYS probes, there were 2,332 differentially methylated CpG sites (DMSs) between sexes, which were enriched within brain modules of co-methylated CpGs during brain development and also differentially methylated in the brains of boys and girls. Genes associated with the DMSs were enriched for neurodevelopmental disorders, particularly for CpG sites found differentially methylated in brain tissue between patients with schizophrenia and controls. Moreover, the DMS had an overlap of 890 (38%) CpG sites with a cohort submitted to toxic exposition during gestation. This study supports the evidences that sex differences in DNA methylation of autosomes act as a primary driver of sex differences that are found in psychiatric outcomes.
- Comparison of Two Methods of RNA Extraction from Formalin-Fixed Paraffin-Embedded Tissue Specimens(2014) GOUVEIA, Gisele Rodrigues; FERREIRA, Suzete Cleusa; FERREIRA, Jerenice Esdras; SIQUEIRA, Sheila Aparecida Coelho; PEREIRA, JulianaThe present study aimed to compare two different methods of extracting RNA from formalin-fixed paraffin-embedded (FFPE) specimens of diffuse large B-cell lymphoma (DLBCL). We further aimed to identify possible influences of variables-such as tissue size, duration of paraffin block storage, fixative type, primers used for cDNA synthesis, and endogenous genes tested-on the success of amplification from the samples. Both tested protocols used the same commercial kit for RNA extraction (the Recover All Total Nucleic Acid Isolation Optimized for FFPE Samples from Ambion). However, the second protocol included an additional step of washing with saline buffer just after sample rehydration. Following each protocol, we compared the RNA amount and purity and the amplification success as evaluated by standard PCR and real-time PCR. The results revealed that the extra washing step added to the RNA extraction process resulted in significantly improved RNA quantity and quality and improved success of amplification from paraffin-embedded specimens.