RENATA ELOAH DE LUCENA FERRETTI-REBUSTINI
Projetos de Pesquisa
Unidades Organizacionais
ENC, EE - Docente
LIM/66, Hospital das Clínicas, Faculdade de Medicina
LIM/22 - Laboratório de Patolologia Cardiovascular, Hospital das Clínicas, Faculdade de Medicina
LIM/66, Hospital das Clínicas, Faculdade de Medicina
LIM/22 - Laboratório de Patolologia Cardiovascular, Hospital das Clínicas, Faculdade de Medicina
37 resultados
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- Low brain-derived neurotrophic factor levels in post-mortem brains of older adults with depression and dementia in a large clinicopathological sample(2018) NUNES, Paula Villela; NASCIMENTO, Camila Fernandes; KIM, Helena Kyunghee; ANDREAZZA, Ana Cristina; BRENTANI, Helena Paula; SUEMOTO, Claudia Kimie; LEITE, Renata Elaine Paraizo; FERRETTI-REBUSTINI, Renata Eloah de Lucena; PASQUALUCCI, Carlos Augusto; NITRINI, Ricardo; GRINBERG, Lea Tenenholz; YONG, Lionel Trevor; JACOB-FILHO, Wilson; LAFER, BenyBackground: Disturbances in peripheral brain-derived neurotrophic factor (BDNF) have been reported in major depressive disorder (MDD). However, there are no studies measuring BDNF levels directly in post-mortem brains of older subjects with MDD and dementia. We aimed to verify if brain BDNF levels were lower in older adults with lifetime history of MDD with and without dementia. Methods: BDNF levels of post-mortem brains from 80 community-dwelling older individuals with lifetime MDD with and without dementia were compared with levels from 80 controls without lifetime MDD. Participants with no reliable close informant, or with prolonged agonal state were excluded. Lifetime MDD was defined as at least one previous episode according to the Structured Clinical Interview for DSM (SCID). Results: BDNF levels were lower in the MDD group with dementia than in participants with dementia and without MDD as confirmed by multivariate analysis adjusted for clinical and cardiovascular risk factors (beta = - 0.106, 95%CI = - 0.204; - 0.009, p = 0.034). No difference was found in the group with MDD without dementia compared with their controls. Limitations: The retrospective assessment of a lifetime history of depression may be subject to information bias and this study only establishes a cross-sectional association between lifetime history of MDD and lower levels of BDNF in patients with dementia. Conclusions: In this community sample of older individuals, lower brain BDNF levels were found in cases with both lifetime MDD and dementia. Low BDNF levels could be a moderator to accelerated brain aging observed in MDD with dementia.
- The influence of age and sex on the absolute cell numbers of the human brain cerebral cortex(2023) CASTRO-FONSECA, Emily; MORAIS, Viviane; SILVA, Camila G. da; WOLLNER, Juliana; FREITAS, Jaqueline; MELLO-NETO, Arthur F.; OLIVEIRA, Luiz E.; OLIVEIRA, Vilson C. de; LEITE, Renata E. P.; ALHO, Ana T.; RODRIGUEZ, Roberta D.; FERRETTI-REBUSTINI, Renata E. L.; SUEMOTO, Claudia K.; JACOB-FILHO, Wilson; NITRINI, Ricardo; PASQUALUCCI, Carlos A.; GRINBERG, Lea T.; TOVAR-MOLL, Fernanda; LENT, RobertoThe human cerebral cortex is one of the most evolved regions of the brain, responsible for most higher-order neural functions. Since nerve cells (together with synapses) are the processing units underlying cortical physiology and morphology, we studied how the human neocortex is composed regarding the number of cells as a function of sex and age. We used the isotropic fractionator for cell quantification of immunocytochemically labeled nuclei from the cerebral cortex donated by 43 cognitively healthy subjects aged 25-87 years old. In addition to previously reported sexual dimorphism in the medial temporal lobe, we found more neurons in the occipital lobe of men, higher neuronal density in women's frontal lobe, but no sex differences in the number and density of cells in the other lobes and the whole neocortex. On average, the neocortex has similar to 10.2 billion neurons, 34% in the frontal lobe and the remaining 66% uniformly distributed among the other 3 lobes. Along typical aging, there is a loss of non-neuronal cells in the frontal lobe and the preservation of the number of neurons in the cortex. Our study made possible to determine the different degrees of modulation that sex and age evoke on cortical cellularity.
- 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.
- Elaboração e validação da Escala Brasileira de Percepção sobre Eutanásia(2023) MURAKAMI, Beatriz Murata; FERRETTI-REBUSTINI, Renata Eloah de Lucena; AMENDOLA, Fernanda; ALMEIDA, Fabiane de AmorimAbstract This research elaborated an instrument to identify nurses’ perception on euthanasia and test its content validity, response process, internal structure and reliability evidences. A psychometric study was conducted through evaluation by a committee of judges, pre-test, and validation. The latter step included 821 nurses. Exploratory and confirmatory factor analyses were performed. A total of 55 items were elaborated based on a literature review. After review by judges and applying the suggested changes, all items showed agreement above 80% between evaluators. Exploratory and confirmatory factor analyses indicated a satisfactory fit of a two-dimensional model and good reliability indices (α=0.85; Ω=0.89). The 12-item scale showed good validity and reliability evidences, and can be used to measure nurses’ perception on euthanasia.
- 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.
- Trace element concentration differences in regions of human brain by INAA(2013) SAIKI, M.; LEITE, R. E. P.; GENEZINI, F. A.; GRINBERG, L. T.; FERRETTI, R. E. L.; FARFEL, J. M.; SUEMOTO, C.; PASQUALUCCI, C. A.; JACOB-FILHO, W.Studies have shown that there is a potential relationship between the levels of trace elements in cerebral tissues and neurological disorders. However, there are few publications available on the elemental composition of these tissues as well as for different regions of the brain. The aim of this study was to investigate trace element differences in various regions of the human brain from an elderly population of normal individuals. Brain samples from 31 individuals of both genders, aged 51-95 years were provided by the Brain Bank of the Brazilian Aging Study Group of the So Paulo University, Medical School. The tissues from the regions of the hippocampus, cerebellum and frontal, parietal, temporal, occipital cortex were dissected using a titanium knife, ground, freeze-dried and then analyzed by instrumental neutron activation analysis (INAA). Samples and element standards were irradiated with a neutron flux at the IEA-R1 nuclear research reactor for Br, Fe, K, Na, Rb, Se and Zn determinations. One-way ANOVA test (p < 0.05) was used to compare the results which showed significant differences for several elements among the brain regions. Most of our brain analysis results agreed with the literature data. The results were also submitted for brain region classification by cluster analysis.
- Is Olfactory Epithelium Biopsy Useful for Confirming Alzheimer's Disease?(2019) GODOY, Maria Dantas Costa Lima; FORNAZIERI, Marco Aurelio; DOTY, Richard L.; PINNA, Fabio de Rezende; FARFEL, Jose Marcelo; SANTOS, Glaucia Bento dos; MOLINA, Mariana; FERRETTI-REBUSTINI, Renata E. L.; LEITE, Renata E. P.; SUEMOTO, Claudia K.; GRINBERG, Lea T.; PASCRALUCCI, Carlos A. G.; VOEGELS, Richard Louis; NITRINI, Ricardo; JACOB FILHO, WilsonObjectives: The clinical symptoms of Alzheimer's disease (AD) are preceded by a long asymptomatic period associated with ""silent"" deposition of aberrant paired helical filament (PHF)-tau and amyloid-beta proteins in brain tissue. Similar depositions have been reported within the olfactory epithelium (OE), a tissue that can be biopsied in vivo. The degree to which such biopsies are useful in identifying AD is controversial. This postmortem study had 3 main goals: first, to quantify the relative densities of AD-related proteins in 3 regions of the olfactory neuroepithelium, namely, the nasal septum, middle turbinate, and superior turbinate; second, to establish whether such densities are correlated among these epithelial regions as well as with semi-quantitative ratings of general brain cortex pathology; and third, to evaluate correlations between the protein densities and measures of antemortem cognitive function. Methods: Postmortem blocks of olfactory mucosa were obtained from 12 AD cadavers and 24 controls and subjected to amyloid-beta and PHF-tau immunohistochemistry. Results: We observed marked heterogeneity in the presence of the biomarkers of tau and amyloid-beta among the targeted olfactory epithelial regions. No significant difference was observed between the cadavers with AD and the controls regarding the concentration of these proteins in any of these epithelial regions. Only one correlation significant was evident, namely, that between the tau protein densities of the middle and the upper turbinate (r = .58, P = .002). Conclusion: AD-related biomarker heterogeneity, which has not been previously demonstrated, makes comparisons across studies difficult and throws into question the usefulness of OE amyloid-beta and PHF-tau biopsies in detecting AD.
- Atherosclerosis and Dementia A Cross-Sectional Study With Pathological Analysis of the Carotid Arteries(2011) SUEMOTO, Claudia K.; NITRINI, Ricardo; GRINBERG, Lea T.; FERRETTI, Renata E. L.; FARFEL, Jose M.; LEITE, Renata E. P.; MENEZES, Paulo R.; FREGNI, Felipe; JACOB-FILHO, Wilson; PASQUALUCCI, Carlos A.Background and Purpose-Previous ultrasound-based studies have shown an association between carotid artery atherosclerosis and dementia. Our aim was to investigate this association using postmortem examination. Methods-Postmortem morphometric measurements of carotid stenosis and intima-media thickness were performed in individuals with dementia (n = 112) and control subjects (n = 577). Multivariate logistic regression models were applied. Results-High-grade left internal carotid stenosis (>= 70%) was associated with increased odds for dementia (OR, 2.30; 95% CI, 1.14-4.74; P = 0.02). Intima-media thickness was not associated with dementia. Conclusions-The likelihood of dementia is increased with high-grade left internal carotid artery atherosclerosis after adjusting for demographic and cardiovascular risk factors. (Stroke. 2011; 42: 3614-3615.)
conferenceObject Inflammation in the Perivascular Adipose Tissue is Associated With Coronary Artery Disease: An Autopsy Study(2015) FARIAS, Daniela S.; PASQUALUCCI, Carlos A.; NISHIZAWA, Aline; SILVA, Luiz F.; CAMPOS, Fernanda M.; SILVA, Karen C.; CUELHO, Anderson; LEITE, Renata E.; FERRETTI-REBUSTINI, Renata E.; GRINBERG, Lea T.; FARREL, Jose M.; JACOB-FILHO, Wilson; SUEMOTO, Claudia K.- Factors associated with brain volume in major depression in older adults without dementia: results from a large autopsy study(2018) NUNES, Paula Villela; SUEMOTO, Claudia Kimie; LEITE, Renata Elaine Paraizo; FERRETTI-REBUSTINI, Renata Eloah de Lucena; PASQUALUCCI, Carlos Augusto; NITRINI, Ricardo; FARFEL, Jose Marcelo; OLIVEIRA, Katia Cristina de; GRINBERG, Lea Tenenholz; COSTA, Nicole Rezende da; NASCIMENTO, Camila Fernandes; SALMASI, Faraz; KIM, Helena Kyunghee; YOUNG, Lionel Trevor; JACOB-FILHO, Wilson; LAFER, BenyObjectiveWe examined brain volume and atrophy in individuals with major depressive disorder (MDD) without dementia that were referred to a large autopsy service. We also examined potential risk factors for brain atrophy, including demographics and clinical variables. MethodsIn this study, 1373 participants (787 male) aged 50years or older who died from natural causes were included. Participants with no reliable informant, with cognitive impairment or dementia, with a medical history of severe chronic disease, or with prolonged agonal state were excluded. Presence of MDD at least once in their lifetime was defined according to the Structured Clinical Interview for DSM. Brain volume was measured immediately after removal from the skull. ResultsMean age at death was 68.611.6, and MDD was present in 185 (14%) individuals. Smaller brain volume was associated with older age (p<0.001), lower education (years; p<0.001), hypertension (p=0.001), diabetes (p=0.006), and female gender (p<0.001). In the multivariate analysis adjusted for sociodemographics and cardiovascular risk factors, smaller brain volume was not associated with major depression (=-0.86, 95% CI=-26.50 to 24.77, p=0.95). ConclusionsIn this large autopsy study of older adults, MDD was not associated with smaller brain volumes. Regardless of the presence of MDD, in this sample of older adults without dementia, we found that smaller brain volumes were associated with risk factors for brain neurodegeneration such as older age, diabetes, hypertension, and lower education.