LIM/15 - Laboratório de Investigação em Neurologia
URI Permanente desta comunidade
O Laboratório de Investigação em Neurologia é ligado ao Departamento de Neurologia da Faculdade de Medicina da Universidade de São Paulo (FMUSP).
Linhas de pesquisa: líquido cefalorraquiano; neuroinfecção; demências; biologia molecular e celular dos tumores do sistema nervoso central; miopatias; anticonvulsivantes; estresse oxidativo em distúrbios cognitivos e do comportamento; estimulação magnética transcraniana.
Site oficial: http://limhc.fm.usp.br/portal/lim15-laboratorio-de-investigacao-em-neurologia/
Linhas de pesquisa: líquido cefalorraquiano; neuroinfecção; demências; biologia molecular e celular dos tumores do sistema nervoso central; miopatias; anticonvulsivantes; estresse oxidativo em distúrbios cognitivos e do comportamento; estimulação magnética transcraniana.
Site oficial: http://limhc.fm.usp.br/portal/lim15-laboratorio-de-investigacao-em-neurologia/
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- LIM/15 - Laboratório de Investigação em Neurologia
- LIM/15 - Laboratório de Investigação em Neurologia
- LIM/15 - Laboratório de Investigação em Neurologia
Submissões Recentes
LOXL3 knock out affects pathways which involve cytoskeleton regulation, proliferation and apoptosis in glioblastoma cells
(2023) LAURENTINO, Talita S.; SOARES, Roseli S.; LERARIO, Antonio M.; MARIE, Suely K.; OBA-SHINJO, Sueli Mieko
PATIENT AND CAREGIVER SPINAL MUSCULAR ATROPHY (SMA) TREATMENT ATTRIBUTE PREFERENCES IN LATIN AMERICA
(2023) SAENZ, V; CHLISTALLA, M.; CARLOS, N.; CASTIGLIONI, Toledo C.; SOLEDAD, Monges M.; SERVAIS, L.; ZANOTELI, E.
Hemifacial Spasm: gene expression and immunohistochemical analysis
(2023) GAMEIRO, Gustavo; OSAKI, Midori; OSAKI, Teissy; CAMPOS, Eliene; MARIE, Suely; OSAKI, Tammy
Metabolic and Structural Signatures in Corticobasal Syndrome: A Multimodal PET/MRI Study
(2021) CARNEIRO, G. C.; PARMERA, J. B.; ALMEIDA, I. J.; OLIVEIRA, M. C. B.; SILAGI, M. L.; STUDART-NETO, A.; ONO, C. R.; BARBOSA, E. R.; NITRINI, R.; BUCHPIGUEL, C. A.; BRUCKI, S. M. D.; COUTINHO, A. M.
Epigenetic dedifferentiation as a therapeutic strategy in adrenal cancer
(2023) MOHAN, Dipika R.; BORGES, Kleiton S.; FINCO, Isabella; LAPENSEE, Christopher R.; REGE, Juilee; LITTLE, Donald W.; ELSE, Tobias; ALMEIDA, Madson Q.; DANG, Derek; HAGGERTY-SKEANS, James; LATRONICO, Ana Claudia; MENDONCA, Berenice B.; AUCHUS, Richard J.; RAINEY, William E.; MARIE, Suely K.; GIORDANO, Thomas J.; VENNETI, Sriram; FRAGOSO, Maria Candida B.; BREAULT, David T.; LERARIO, Antonio M.; HAMMER, Gary D.
Cerebral venous sinus thrombosis due to vaccine-induced immune thrombotic thrombocytopenia in middle-income countries
(2023) MUNCKHOF, Anita van de; BORHANI-HAGHIGHI, Afshin; AARON, Sanjith; KRZYWICKA, Katarzyna; KAMMEN, Mayte Sanchez van; CORDONNIER, Charlotte; KLEINIG, Timothy J.; FIELD, Thalia S.; POLI, Sven; LEMMENS, Robin; SCUTELNIC, Adrian; LINDGREN, Erik; DUAN, Jiangang; ARSLAN, Yildiz; GORP, Eric C. M. van; HOVINGA, Johanna A. Kremer; GUENTHER, Albrecht; JOOD, Katarina; TATLISUMAK, Turgut; PUTAALA, Jukka; HELDNER, Mirjam R.; ARNOLD, Marcel; SOUSA, Diana Aguiar de; WASAY, Mohammad; ARAUZ, Antonio; CONFORTO, Adriana Bastos; FERRO, Jose M.; COUTINHO, Jonathan M.
Background: Adenovirus-based COVID-19 vaccines are extensively used in low- and middle-income countries (LMICs). Remarkably, cases of cerebral venous sinus thrombosis due to vaccine-induced immune thrombotic thrombocytopenia (CVST-VITT) have rarely been reported from LMICs. Aims: We studied the frequency, manifestations, treatment, and outcomes of CVST-VITT in LMICs. Methods: We report data from an international registry on CVST after COVID-19 vaccination. VITT was classified according to the Pavord criteria. We compared CVST-VITT cases from LMICs to cases from high-income countries (HICs). Results: Until August 2022, 228 CVST cases were reported, of which 63 were from LMICs (all middle-income countries [MICs]: Brazil, China, India, Iran, Mexico, Pakistan, Turkey). Of these 63, 32 (51%) met the VITT criteria, compared to 103 of 165 (62%) from HICs. Only 5 of the 32 (16%) CVST-VITT cases from MICs had definite VITT, mostly because anti-platelet factor 4 antibodies were often not tested. The median age was 26 (interquartile range [IQR] 20-37) versus 47 (IQR 32-58) years, and the proportion of women was 25 of 32 (78%) versus 77 of 103 (75%) in MICs versus HICs, respectively. Patients from MICs were diagnosed later than patients from HICs (1/32 [3%] vs. 65/103 [63%] diagnosed before May 2021). Clinical manifestations, including intracranial hemorrhage, were largely similar as was intravenous immunoglobulin use. In-hospital mortality was lower in MICs (7/31 [23%, 95% confidence interval (CI) 11-40]) than in HICs (44/102 [43%, 95% CI 34-53], p = 0.039). Conclusions: The number of CVST-VITT cases reported from LMICs was small despite the widespread use of adenoviral vaccines. Clinical manifestations and treatment of CVST-VITT cases were largely similar in MICs and HICs, while mortality was lower in patients from MICs.
Association between APOE-ε4 allele and cognitive function is mediated by Alzheimer's disease pathology: a population-based autopsy study in an admixed sample
(2023) PARADELA, Regina Silva; JUSTO, Alberto Fernando Oliveira; PAES, Vitor Ribeiro; LEITE, Renata E. P.; PASQUALUCCI, Carlos A.; GRINBERG, Lea T.; NASLAVSKY, Michel Satya; ZATZ, Mayana; NITRINI, Ricardo; JACOB-FILHO, Wilson; SUEMOTO, Claudia Kimie
Background: Apolipoprotein E epsilon 4 allele (APOE-epsilon 4) is the main genetic risk factor for late-onset Alzheimer's disease (AD) and may impact cognitive function also via other neuropathological lesions. However, there is limited evidence available from diverse populations, as APOE associations with dementia seem to differ by race. Therefore, we aimed to evaluate the pathways linking APOE-epsilon 4 to cognitive abilities through AD and non-AD neuropathology in an autopsy study with an admixed sample.Methods: Neuropathological lesions were evaluated following international criteria using immunohistochemistry. Participants were classified into APOE-epsilon 4 carriers (at least one epsilon 4 allele) and non-carriers. Cognitive abilities were evaluated by the Clinical Dementia Rating Scale sum of boxes. Mediation analyses were conducted to assess the indirect association of APOE-epsilon 4 with cognition through AD-pathology, lacunar infarcts, hyaline arteriosclerosis, cerebral amyloid angiopathy (CAA), Lewy body disease (LBD), and TAR DNA-binding protein 43 (TDP-43).Results: We included 648 participants (mean age 75 +/- 12 years old, mean education 4.4 +/- 3.7 years, 52% women, 69% White, and 28% APOE-epsilon 4 carriers). The association between APOE-epsilon 4 and cognitive abilities was mediated by neurofibrillary tangles (beta = 0.88, 95% CI = 0.45; 1.38, p < 0.001) and neuritic plaques (beta = 1.36, 95% CI = 0.86; 1.96, p < 0.001). Lacunar infarcts, hyaline arteriosclerosis, CAA, LBD, and TDP-43 were not mediators in the pathway from APOE-epsilon 4 to cognition.Conclusion: The association between APOE-epsilon 4 and cognitive abilities was partially mediated by AD-pathology. On the other hand, cerebrovascular lesions and other neurodegenerative diseases did not mediate the association between APOE-epsilon 4 and cognition.
Biomarkers for dementia in Latin American countries: Gaps and opportunities
(2023) PARRA, Mario A.; ORELLANA, Paulina; LEON, Tomas; VICTORIA, Cabello G.; HENRIQUEZ, Fernando; GOMEZ, Rodrigo; AVALOS, Constanza; DAMIAN, Andres; SLACHEVSKY, Andrea; IBANEZ, Agustin; ZETTERBERG, Henrik; TIJMS, Betty M.; YOKOYAMA, Jennifer S.; PINA-ESCUDERO, Stefanie D.; COCHRAN, J. Nicholas; MATALLANA, Diana L.; ACOSTA, Daisy; ALLEGRI, Ricardo; ARIAS-SUAREZ, Bianca P.; BARRA, Bernardo; BEHRENS, Maria Isabel; BRUCKI, SoniaM. D.; BUSATTO, Geraldo; CARAMELLI, Paulo; CASTRO-SUAREZ, Sheila; CONTRERAS, Valeria; CUSTODIO, Nilton; DANSILIO, Sergio; CRUZ-PUEBLA, Myriam De la; SOUZA, Leonardo Cruz de; DIAZ, Monica M.; DUQUE, Lissette; FARIAS, Gonzalo A.; FERREIRA, Sergio T.; GUIMET, Nahuel Magrath; KMAID, Ana; LIRA, David; LOPERA, Francisco; MEZA, Beatriz Mar; MIOTTO, Eliane C.; NITRINI, Ricardo; NUNEZ, Alberto; O'NEILL, Santiago; OCHOA, John; PINTADO-CAIPA, Maritza; RESENDE, Elisa de Paula Franca; RISACHER, Shannon; ROJAS, Luz Angela; SABAJ, Valentina; SCHILLING, Lucas; SELLEK, Allis F.; SOSA, Ana; TAKADA, Leonel T.; TEIXEIRA, Antonio L.; UNAUCHO-PILALUMBO, Martha; DURAN-ANIOTZ, Claudia
Limited knowledge on dementia biomarkers in Latin American and Caribbean (LAC) countries remains a serious barrier. Here, we reported a survey to explore the ongoing work, needs, interests, potential barriers, and opportunities for future studies related to biomarkers. The results show that neuroimaging is the most used biomarker (73%), followed by genetic studies (40%), peripheral fluids biomarkers (31%), and cerebrospinal fluid biomarkers (29%). Regarding barriers in LAC, lack of funding appears to undermine the implementation of biomarkers in clinical or research settings, followed by insufficient infrastructure and training. The survey revealed that despite the above barriers, the region holds a great potential to advance dementia biomarkers research. Considering the unique contributions that LAC could make to this growing field, we highlight the urgent need to expand biomarker research. These insights allowed us to propose an action plan that addresses the recommendations for a biomarker framework recently proposed by regional experts.
The past, present and future of Alzheimer's disease - part 1: the past
(2023) NITRINI, Ricardo
Background Alzheimer's disease (AD) was described in 1907, and since then it changed from a relatively rare condition to one of the most prevalent diseases.Objective To describe the evolution of the notions of dementias and AD, and to investigate the reasons for the increase in scientific interest in AD.Methods A historical analysis was carried out on knowledge about dementia, the site of mental activity, the relationships between brain diseases and mental activity, and on the advances in research about AD, since its discovery until the publication of the amyloid cascade hypothesis in 1992. A search was carried out in the National Library of Medicine (PubMed) for scientific articles that included the terms dementia or AD over 50 years, from 1972 to 2021.Results The scientific research on AD increased from 615 papers with the term AD in the first decade (1972-1981), to 100,028 papers in the last decade (2012-2021): an increase of 162.6 times whereas publications with the term dementia increased 28.6 times in the same period. In the 1960s and 1970s, a consensus was reached that AD is responsible for the majority of cases of dementia previously known as senile dementia. In the 1980s, beta-amyloid peptide was identified in the core of the senile plaque, hyperphosphorylated tau protein was found in neurofibrillary tangles, and a mutation was discovered in a hereditary form of AD.Conclusion The expansion of the concept of AD to include senile dementia, and the discoveries that occurred in the 1980s greatly expanded research in AD.
A novel program of infiltrative control in astrocytomas: ADAM23 depletion promotes cell invasion by activating γ-secretase complex
(2023) JANDREY, Elisa Helena Farias; BARNABE, Gabriela Filoso; MALDAUN, Marcos; ASPRINO, Paula Fontes; SANTOS, Natalia Cristina dos; INOUE, Lilian Tiemi; ROZANSKI, Andrei; GALANTE, Pedro Alexandre Favoretto; MARIE, Suely Kazue Nagahashi; OBA-SHINJO, Sueli Mieko; SANTOS, Tiago Goss dos; CHAMMAS, Roger; LANCELLOTTI, Carmen Lucia Penteado; FURNARI, Frank B.; CAMARGO, Anamaria Aranha; COSTA, Erico Tosoni
Background. Infiltration is a life-threatening growth pattern in malignant astrocytomas and a significant cause of therapy resistance. It results in the tumor cell spreading deeply into the surrounding brain tissue, fostering tumor recurrence and making complete surgical resection impossible. We need to thoroughly understand the mechanisms underlying diffuse infiltration to develop effective therapies.Methods We integrated in vitro and in vivo functional assays, RNA sequencing, clinical, and expression information from public data sets to investigate the role of ADAM23 expression coupling astrocytoma's growth and motility.Results. ADAM23 downregulation resulted in increased infiltration, reduced tumor growth, and improved overall survival in astrocytomas. Additionally, we show that ADAM23 deficiency induces gamma-secretase (GS) complex activity, contributing to the production and deposition of the Amyloid-beta and release of NICD. Finally, GS ablation in ADAM23-low astrocytomas induced a significant inhibitory effect on the invasive programs.Conclusions. Our findings reveal a role for ADAM23 in regulating the balance between cell proliferation and invasiveness in astrocytoma cells, proposing GS inhibition as a therapeutic option in ADAM23 low-expressing astrocytomas.