RENATA ELAINE PARAIZO LEITE
Projetos de Pesquisa
Unidades Organizacionais
LIM/22 - Laboratório de Patolologia Cardiovascular, Hospital das Clínicas, Faculdade de Medicina
14 resultados
Resultados de Busca
Agora exibindo 1 - 10 de 14
- 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.
- Hyperphosphorylated Tau in Mesial Temporal Lobe Epilepsy: a Neuropathological and Cognitive Study(2023) TOSCANO, Eliana C. B.; VIEIRA, Erica L. M.; GRINBERG, Lea T.; ROCHA, Natalia P.; BRANT, Joseane A. S.; PARADELA, Regina S.; GIANNETTI, Alexandre V.; SUEMOTO, Claudia K.; LEITE, Renata E. P.; NITRINI, Ricardo; RACHID, Milene A.; TEIXEIRA, Antonio L.Temporal lobe epilepsy (TLE) often courses with cognitive deficits, but its underlying neuronal basis remains unclear. Confluent data suggest that epilepsy share pathophysiological mechanisms with neurodegenerative diseases. However, as most studies analyze subjects 60 years old and older, it is challenging to rule out that neurodegenerative changes arise from age-related mechanisms rather than epilepsy in these individuals. To fill this gap, we conducted a neuropathological investigation of the hippocampal formation of 22 adults with mesial TLE and 20 age-and sex-matched controls (both younger than 60 years). Moreover, we interrogated the relationship between these neuropathological metrics and cognitive performance. Hippocampal formation extracted from patients with drug-resistant mesial TLE undergoing surgery and postmortem non-sclerotic hippocampal formation of clinically and neuropathologically controls underwent immunohistochemistry against amyloid beta (A beta), hyperphosphorylated tau (p-tau), and TAR DNA-binding protein-43 (TDP-43) proteins, followed by quantitative analysis. Patients underwent a comprehensive neuropsychological evaluation prior to surgery. TLE hippocampi showed a significantly higher burden of p-tau than controls, whereas A beta deposits and abnormal inclusions of TDP-43 were absent in both groups. Patients with hippocampal sclerosis (HS) type 2 had higher immunostaining for p-tau than patients with HS type 1. In addition, p-tau burden was associated with impairment in attention tasks and seizures frequency. In this series of adults younger than 60 years-old, the increase of p-tau burden associated with higher frequency of seizures and attention impairment suggests the involvement of tau pathology as a potential contributor to cognitive deficits in mesial TLE.
- Increased levels of TAR DNA-binding protein 43 in the hippocampus of subjects with bipolar disorder: a postmortem study(2022) NASCIMENTO, Camila; V, Paula Nunes; KIM, Helena K.; LEITE, Renata E. P.; RODRIGUEZ, Roberta D.; OLIVEIRA, Katia Cristina De; BRENTANI, Helena P.; JACOB-FILHO, Wilson; NITRINI, Ricardo; PASQUALUCCI, Carlos A.; GRINBERG, Lea T.; SUEMOTO, Claudia K.; LAFER, BenyBipolar disorder shares symptoms and pathological pathways with other neurodegenerative diseases, including frontotemporal dementia (FTD). Since TAR DNA-binding protein 43 (TDP-43) is a neuropathological marker of frontotemporal dementia and it is involved in synaptic transmission, we explored the role of TDP-43 as a molecular feature of bipolar disorder (BD). Homogenates were acquired from frozen hippocampus of postmortem brains of bipolar disorder subjects. TDP-43 levels were quantified using an ELISA-sandwich method and compared between the postmortem brains of bipolar disorder subjects and age-matched control group. We found higher levels of TDP-43 protein in the hippocampus of BD (n = 15) subjects, when compared to controls (n = 15). We did not find associations of TDP-43 with age at death, postmortem interval, or age of disease onset. Our results suggest that protein TDP-43 may be potentially implicated in behavioral abnormalities seen in BD. Further investigation is needed to validate these findings and to examine the role of this protein during the disease course and mood states.
- Unrevealing the role of a frontotemporal dementia protein (TDP-43 protein) in bipolar disorder(2019) NASCIMENTO, C.; VILLELA, P. Nunes; KIM, H. Kyunghee; OLIVEIRA, K. De; LEITE, R. E. Paraizo; FERRETTI-REBUSTINI, R. E. D. L.; GRINBERG, L. T.; SUEMOTO, C. K.; PASQUALUCCI, C. A.; NITRINI, R.; JACOB-FILHO, W.; BRENTANI, H. P.; LAFER, B.
conferenceObject Synaptic proteasome is inhibited in Alzheimer's disease models and is associated with memory impairment in mice(2023) RIBEIRO, Felipe; COZACHENCO, Danielle; FORTUNA, Juliana; FREITAS, Guilherme de; SOUZA, Jorge de; LEITE, Renata; SUEMOTO, Claudia; GRINBERG, Lea; FELICE, Fernanda de; LOURENCO, Mychael; FERREIRA, Sergio- 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.
conferenceObject 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.- Alzheimer's disease brain-derived extracellular vesicles reveal altered synapse-related proteome and induce cognitive impairment in mice(2023) BODART-SANTOS, Victor; PINHEIRO, Lisandra S.; SILVA-JUNIOR, Almir J. da; FROZA, Rudimar L.; AHRENS, Rosemary; GONCALVES, Rafaella A.; ANDRADE, Mayara M.; CHEN, Yan; ALCANTARA, Carolina de Lima; GRINBERG, Lea T.; LEITE, Renata E. P.; FERREIRA, Sergio T.; FRASER, Paul E.; FELICE, Fernanda G. DeINTRODUCTIONExtracellular vesicles (EVs) have been implicated in the spread of neuropathology in Alzheimer's disease (AD), but their involvement in behavioral outcomes linked to AD remains to be determined. METHODSEVs isolated from post mortem brain tissue from control, AD, or frontotemporal dementia (FTD) donors, as well as from APP/PS1 mice, were injected into the hippocampi of wild-type (WT) or a humanized Tau mouse model (hTau/mTauKO). Memory tests were carried out. Differentially expressed proteins in EVs were assessed by proteomics. RESULTSBoth AD-EVs and APP/PS1-EVs trigger memory impairment in WT mice. We further demonstrate that AD-EVs and FTD-EVs carry Tau protein, present altered protein composition associated with synapse regulation and transmission, and trigger memory impairment in hTau/mTauKO mice. DISCUSSIONResults demonstrate that AD-EVs and FTD-EVs have negative impacts on memory in mice and suggest that, in addition to spreading pathology, EVs may contribute to memory impairment in AD and FTD. HighlightsA beta was detected in EVs from post mortem AD brain tissue and APP/PS1 mice.Tau was enriched in EVs from post mortem AD, PSP and FTD brain tissue.AD-derived EVs and APP/PS1-EVs induce cognitive impairment in wild-type (WT) mice.AD- and FTD-derived EVs induce cognitive impairment in humanized Tau mice.Proteomics findings associate EVs with synapse dysregulation in tauopathies.
- Low brain-derived neurotrophic factor levels in post-mortem brains is associated with sub-syndromic neuropsychiatric symptoms(2019) NUNES, P. V.; NASCIMENTO, C. F.; KIM, H. K.; ANDREAZZA, A.; BRENTANI, H. P.; SUEMOTO, C. K.; LEITE, R. E. P.; FERRETTI-REBUSTINI, R. E. D. L.; PASQUALUCCI, C. A.; NITRINI, R.; GRINBERG, L. T.; YOUNG, L. T.; JACOB-FILHO, W.; LAFER, B.
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.