JOSE MARCELO FARFEL
Projetos de Pesquisa
Unidades Organizacionais
Departamento de Ortopediae Traumatologia, Faculdade de Medicina - Docente
LIM/22 - Laboratório de Patolologia Cardiovascular, Hospital das Clínicas, Faculdade de Medicina
LIM/22 - Laboratório de Patolologia Cardiovascular, Hospital das Clínicas, Faculdade de Medicina
9 resultados
Resultados de Busca
Agora exibindo 1 - 9 de 9
- 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.
- Repair of Oxidative DNA Damage, Cell-Cycle Regulation and Neuronal Death May Influence the Clinical Manifestation of Alzheimer's Disease(2014) SILVA, Aderbal R. T.; SANTOS, Ana Cecilia Feio; FARFEL, Jose M.; GRINBERG, Lea T.; FERRETTI, Renata E. L.; CAMPOS, Antonio Hugo Jose Froes Marques; CUNHA, Isabela Werneck; BEGNAMI, Maria Dirlei; ROCHA, Rafael M.; CARRARO, Dirce M.; PEREIRA, Carlos Alberto de Braganca; JACOB-FILHO, Wilson; BRENTANI, HelenaAlzheimer's disease (AD) is characterized by progressive cognitive decline associated with a featured neuropathology (neuritic plaques and neurofibrillary tangles). Several studies have implicated oxidative damage to DNA, DNA repair, and altered cell-cycle regulation in addition to cell death in AD post-mitotic neurons. However, there is a lack of studies that systematically assess those biological processes in patients with AD neuropathology but with no evidence of cognitive impairment. We evaluated markers of oxidative DNA damage (8-OHdG, H2AX), DNA repair (p53, BRCA1, PTEN), and cell-cycle (Cdk1, Cdk4, Cdk5, Cyclin B1, Cyclin D1, p(27Kip1), phospho-Rb and E2F1) through immunohistochemistry and cell death through TUNEL in autopsy hippocampal tissue samples arrayed in a tissue microarray (TMA) composed of three groups: I) ""clinical-pathological AD"" (CP-AD) - subjects with neuropathological AD (Braak >= IV and CERAD = B or C) and clinical dementia (CDR >= 2, IQCODE >= 3.8); II) ""pathological AD"" (P-AD) - subjects with neuropathological AD (Braak >= IV and CERAD = B or C) and without cognitive impairment (CDR 0, IQCODE < 3.2); and III) ""normal aging"" (N) - subjects without neuropathological AD (Braak <= II and CERAD 0 or A) and with normal cognitive function (CDR 0, IQCODE<3.2). Our results show that high levels of oxidative DNA damage are present in all groups. However, significant reductions in DNA repair and cell-cycle inhibition markers and increases in cell-cycle progression and cell death markers in subjects with CP-AD were detected when compared to both P-AD and N groups, whereas there were no significant differences in the studied markers between P-AD individuals and N subjects. This study indicates that, even in the setting of pathological AD, healthy cognition may be associated with a preserved repair to DNA damage, cell-cycle regulation, and cell death in post-mitotic neurons.
conferenceObject TRANSCRIPTOME STUDY IN STRIATUM OF OBSESSIVE COMPULSIVE DISORDERS (POSTMORTEM STUDY)(2017) LISBOA, Bianca; OLIVEIRA, Katia de; LIMA, Luzia Carreira; PUGA, Renato; RIBEIRO, Gustavo; TAHIRA, Ana; FARFEL, Jose Marcelo; FERRETTI-REBUSTINI, Renata Eloah de Lucena; JACOB-FILHO, Wilson; MIGUEL, Euripedes Constantino; PAULS, David; SHAVITT, Roseli; HOEXTER, Marcelo; PEREIRA, Carlos Alberto de Braganca; BRENTANI, HelenaconferenceObject Transactive response DNA-binding protein 43 as a neuromarker of bipolar disorder(2018) NASCIMENTO, C.; VILLELA, P. Nunes; OLIVEIRA, K. C. De; BARBOSA, A.; KIM, H. Kyunghee; MORETTO, A. C.; LEITE, R. E. Paraizo; FERRETTI-REBUSTINI, R. Eloah de Lucena; GRINBERG, L. Tenenholz; SUEMOTO, C. Kimie; FARFEL, J. M.; PASQUALUCCI, C. A.; BRENTANI, H. P.; NITRINI, R.; JACOB-FILHO, W.; LAFER, B.- Layer-specific reduced neuronal density in the orbitofrontal cortex of older adults with obsessive-compulsive disorder(2019) OLIVEIRA, Katia Cristina de; GRINBERG, Lea Tenenholz; HOEXTER, Marcelo Queiroz; BRENTANI, Helena; SUEMOTO, Claudia Kimie; NERY, Fabiano Goncalves; LIMA, Luzia Carreira; ALHO, Ana Tereza Di Lorenzo; FARFEL, Jose Marcelo; FERRETTI-REBUSTINI, Renata Eloah de Lucena; LEITE, Renata Elaine Paraizo; MORETTO, Ariane Cristine; SILVA, Alexandre Valotta da; LAFER, Beny; MIGUEL, Euripedes Constantino; NITRINI, Ricardo; JACOB-FILHO, Wilson; HEINSEN, Helmut; PASQUALUCCI, Carlos AugustoNeurobiological models have provided consistent evidence of the involvement of cortical-subcortical circuitry in obsessive-compulsive disorder (OCD). The orbitofrontal cortex (OFC), involved in motivation and emotional responses, is an important regulatory node within this circuitry. However, OFC abnormalities at the cellular level have so far not been studied. To address this question, we have recruited a total of seven senior individuals from the Sao Paulo Autopsy Services who were diagnosed with OCD after an extensive post-mortem clinical evaluation with their next of kin. Patients with cognitive impairment were excluded. The OCD cases were age- and sex-matched with 7 control cases and a total of 14 formalin-fixed, serially cut, and gallocyanin-stained hemispheres (7 subjects with OCD and 7 controls) were analyzed stereologically. We estimated laminar neuronal density, volume of the anteromedial (AM), medial orbitofrontal (MO), and anterolateral (AL) areas of the OFC. We found statistically significant layer- and region-specific lower neuron densities in our OCD cases that added to a deficit of 25% in AM and AL and to a deficit of 21% in MO, respectively. The volumes of the OFC areas were similar between the OCD and control groups. These results provide evidence of complex layer and region-specific neuronal deficits/loss in old OCD cases which could have a considerable impact on information processing within orbitofrontal regions and with afferent and efferent targets.
conferenceObject Increased levels of TDP-43 protein in postmortem brain tissue of bipolar disorder subjects(2017) NASCIMENTO, C.; KIM, H. Kyunghee; OLIVEIRA, K. Cristina de; MORETTO, A. C.; BRENTANI, H. P.; ANDREAZZA, A.; LEITE, R. E. Paraizo; FERRETTI-REBUSTINI, R. E. D. L.; SUEMOTO, C. Kimie; PASQUALUCCI, C. Augusto; NITRINI, R.; FARFEL, J. M.; JACOB-FILHO, W.; NUNES, P. Villela; LAFER, B.- TRANSCRIPTOME STUDY IN OBSESSIVE COMPULSIVE DISORDERS(2019) LISBOA, Bianca; TAHIRA, Ana Carolina; SANT'ANNA, Arthur; OLIVEIRA, Katia; MIGUEL, Euripedes Constantino; HOEXTER, Marcelo; FARFEL, Jose Marcelo; BRENTANI, Helena
conferenceObject Brain atrophy and major depression in the elderly: results from a large autopsy study(2016) NUNES, P. V.; SUEMOTO, C. K.; LEITE, R. P.; FERRETTI-REBUSTINI, R. E.; PASQUALUCCI, C. A.; NITRINI, R.; BRENTANI, H. P.; FARFEL, J. M.; OLIVEIRA, K. C.; GRINBERG, L. T.; COSTA, N. R.; NASCIMENTO, C. F.; SALMASI, F.; KIM, H.; YOUNG, T.; JACOB FILHO, W.; LAFER, B.- Transcriptional Alterations Related to Neuropathology and Clinical Manifestation of Alzheimer's Disease(2012) SILVA, Aderbal R. T.; GRINBERG, Lea T.; FARFEL, Jose M.; DINIZ, Breno S.; LIMA, Leandro A.; SILVA, Paulo J. S.; FERRETTI, Renata E. L.; ROCHA, Rafael M.; JACOB FILHO, Wilson; CARRARO, Dirce M.; BRENTANI, HelenaAlzheimer's disease (AD) is the most common cause of dementia in the human population, characterized by a spectrum of neuropathological abnormalities that results in memory impairment and loss of other cognitive processes as well as the presence of non-cognitive symptoms. Transcriptomic analyses provide an important approach to elucidating the pathogenesis of complex diseases like AD, helping to figure out both pre-clinical markers to identify susceptible patients and the early pathogenic mechanisms to serve as therapeutic targets. This study provides the gene expression profile of postmortem brain tissue from subjects with clinic-pathological AD (Braak IV, V, or V and CERAD B or C; and CDR >= 1), preclinical AD (Braak IV, V, or VI and CERAD B or C; and CDR = 0), and healthy older individuals (Braak <= II and CERAD 0 or A; and CDR = 0) in order to establish genes related to both AD neuropathology and clinical emergence of dementia. Based on differential gene expression, hierarchical clustering and network analysis, genes involved in energy metabolism, oxidative stress, DNA damage/repair, senescence, and transcriptional regulation were implicated with the neuropathology of AD; a transcriptional profile related to clinical manifestation of AD could not be detected with reliability using differential gene expression analysis, although genes involved in synaptic plasticity, and cell cycle seems to have a role revealed by gene classifier. In conclusion, the present data suggest gene expression profile changes secondary to the development of AD-related pathology and some genes that appear to be related to the clinical manifestation of dementia in subjects with significant AD pathology, making necessary further investigations to better understand these transcriptional findings on the pathogenesis and clinical emergence of AD.