Browsing by Author "Behrens, María Isabel"
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Publication Biomarkers for dementia in Latin American countries: Gaps andopportunities(2023) Parra, Mario A.; Orellana, Paulina; León, Tomas; Victoria, Cabello G.; Henriquez, Fernando; Gomez, Rodrigo; Avalos, Constanza; Damian, Andres; Slachevsky Chonchol, Andrea; Ibañez, Agustin; Zetterberg, Henrik; Tijms, Betty M.; Yokoyama, Jennifer S.; Piña-Escudero, Stefanie D.; Cochran, Nicholas; Matallana, Diana L.; Acosta, Daisy; Allegri, Ricardo; Arias-Suáres, Bianca P.; Barra, Bernardo; Behrens, María Isabel; Brucki, Sonia M.D.; Busatto, Geraldo; Caramelli, Paulo; Castro-Suarez, Sheila; Contreras, Valeria; Custodio, Nilton; Dansilio, Sergio; De la Cruz-Puebla, Myriam; Cruz de Souza, Leonado; Díaz, Monica M.; Duque, Lissette; Farias, Gonzalo A.; Ferreira, Sergio T.; Magrath Guimet, Nahuel; Kmaid, Ana; Lira, David; Lopera, Francisco; Mar Meza, Beatriz; Miotto, Eliane C.Limited knowledge on dementia biomarkers in Latin American and Caribbean (LAC)countries remains a serious barrier. Here, we reported a survey to explore the ongo-ing work, needs, interests, potential barriers, and opportunities for future studiesrelated to biomarkers. The results show that neuroimaging is the most used biomarker(73%), followed by genetic studies (40%), peripheral fluids biomarkers (31%), and cere-brospinal fluid biomarkers (29%). Regarding barriers in LAC, lack of funding appears toundermine the implementation of biomarkers in clinical or research settings, followedby insufficient infrastructure and training. The survey revealed that despite the abovebarriers, 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 allowedus to propose an action plan that addresses the recommendations for a biomarkerframework recently proposed by regional experts.Item Frizzled-1 receptor regulates adult hippocampal neurogenesis(BioMed Central, 2016) Mardones, Muriel; Andaur, Gabriela; Varas-Godoy, Manuel; Henriquez, Jenny; Salech, Felipe; Behrens, María Isabel; Couve, Andres; Inestrosa, Nibaldo; Varela-Nallar, LorenaBACKGROUND: In the adult hippocampus new neurons are continuously generated from neural stem cells (NSCs) present at the subgranular zone of the dentate gyrus. This process is controlled by Wnt signaling, which plays a complex role in regulating multiple steps of neurogenesis including maintenance, proliferation and differentiation of progenitor cells and the development of newborn neurons. Differential effects of Wnt signaling during progression of neurogenesis could be mediated by cell-type specific expression of Wnt receptors. Here we studied the potential role of Frizzled-1 (FZD1) receptor in adult hippocampal neurogenesis. RESULTS: In the adult dentate gyrus, we determined that FZD1 is highly expressed in NSCs, neural progenitors and immature neurons. Accordingly, FZD1 is expressed in cultured adult hippocampal progenitors isolated from mouse brain. To evaluate the role of this receptor in vivo we targeted FZD1 in newborn cells using retroviral-mediated RNA interference. FZD1 knockdown resulted in a marked decrease in the differentiation of newborn cells into neurons and increased the generation of astrocytes, suggesting a regulatory role for the receptor in cell fate commitment. In addition, FZD1 knockdown induced an extended migration of adult-born neurons within the granule cell layer. However, no differences were observed in total dendritic length and dendritic arbor complexity between control and FZD1-deficient newborn neurons. CONCLUSIONS: Our results show that FZD1 regulates specific stages of adult hippocampal neurogenesis, being required for neuronal differentiation and positioning of newborn neurons into the granule cell layer, but not for morphological development of adult-born granule neurons.Item On the role of mining exposure in epigenetic effects in parkinson's disease.(Springer, 2017) Castillo, Sebastian; Muñoz, Patricia; Behrens, María Isabel; Diaz-Grez, Fernando; Segura-Aguilar, JuanTo explore the possible influence of heavy metal mining on incidence of Parkinson's disease (PD), global DNA methylation was assessed in blood samples from a population of PD patients (n = 45) and control subjects (n = 52) in Antofagasta neighborhood, a Chilean city built for exclusive use of mining companies. Comparisons were made with PD subjects (n = 52) and control subjects (n = 59) from Santiago Chile, a city having little association with mining. All subjects were assessed by two neurologists and PD diagnosis was based on UK Parkinson's Disease Society Brain Bank Clinical Diagnostic Criteria. From blood samples obtained from each individual, a decrease in global DNA methylation was observed in PD patients either exposed (49% of control, P < 0.001) or not exposed (47% of control, P < 0.001) to mining activity. Although there was no difference in levels of DNA methylation between PD patients from the two cities, there was a lower level of DNA methylation in control subjects from Santiago versus Antofagasta.Publication Senescence Markers in Peripheral Blood Mononuclear Cells in Amnestic Mild Cognitive Impairment and Alzheimer’s Disease(2022) Salech, Felipe; SanMartín, Carol D.; Concha-Cerda, Jorge; Ponce, Daniela P.; Liabeuf, Gianella; Rogers, Nicole K.; Romero-Hernández, Esteban; Murgas, Paola; Bruna, Bárbara; More, Jamileth; Behrens, María IsabelRecent studies suggest that cellular senescence plays a role in Alzheimer’s Disease (AD) pathogenesis. We hypothesize that cellular senescence markers might be tracked in the peripheral tissues of AD patients. Senescence hallmarks, including altered metabolism, cell-cycle arrest, DNA damage response (DDR) and senescence secretory associated phenotype (SASP), were measured in peripheral blood mononuclear cells (PBMCs) of healthy controls (HC), amnestic mild cognitive impairment (aMCI) and AD patients. Senescence-associated βeta-galactosidase (SA-β-Gal) activity, G0-G1 phase cell-cycle arrest, p16 and p53 were analyzed by flow cytometry, while IL-6 and IL-8 mRNA were analyzed by qPCR, and phosphorylated H2A histone family member X (γH2AX) was analyzed by immunofluorescence. Senescent cells in the brain tissue were determined with lipofuscin staining. An increase in the number of senescent cells was observed in the frontal cortex and hippocampus of advanced AD patients. PBMCs of aMCI patients, but not in AD, showed increased SA-β-Gal compared with HCs. aMCI PBMCs also had increased IL-6 and IL8 mRNA expression and number of cells arrested at G0-G1, which were absent in AD. Instead, AD PBMCs had significantly increased p16 and p53 expression and decreased γH2Ax activity compared with HC. This study reports that several markers of cellular senescence can be measured in PBMCs of aMCI and AD patients.Item The Multi-Partner Consortium to Expand Dementia Research in Latin America (ReDLat): Driving Multicentric Research and Implementation Science(2021) Ibáñez, Agustín; Yokoyama, Jennifer S.; Possin, Katherine L.; Matallana, Diana; Lopera, Francisco; Nitrini, Ricardo; Takada, Leonel T.; Custodio, Nilton; Sosa Ortiz, Ana Luisa; Avila-Funes, José Alberto; Behrens, María Isabel; Slachevsky, Andrea; Myers, Richard M.; Cochran, J. Nicholas; Brusco, Luis Ignacio; Bruno, Martin A.; Brucki, Sonia M. D.; Pina-Escudero, Stefanie Danielle; Oliveira, Maira Okada de; Donnelly Kehoe, Patricio; Santamaria-Garcia, Hernando; Moguilner, Sebastián; Tagliazucchi, Enzo; Maito, Marcelo; Longoria Ibarrola, Erika Mariana; Pintado-Caipa, Maritza; Godoy, Maria Eugenia; Bakman, Vera; Javandel, Shireen; Kosik, Kenneth S.; Valcour, Victor; Miller, Bruce L.; The Latin America the Caribbean Consortium on Dementia (LAC-CD)Dementia is becoming increasingly prevalent in Latin America, contrasting with stable or declining rates in North America and Europe. This scenario places unprecedented clinical, social, and economic burden upon patients, families, and health systems. The challenges prove particularly pressing for conditions with highly specific diagnostic and management demands, such as frontotemporal dementia. Here we introduce a research and networking initiative designed to tackle these ensuing hurdles, the Multi-partner consortium to expand dementia research in Latin America (ReDLat). First, we present ReDLat’s regional research framework, aimed at identifying the unique genetic, social, and economic factors driving the presentation of frontotemporal dementia and Alzheimer’s disease in Latin America relative to the US. We describe ongoing ReDLat studies in various fields and ongoing research extensions. Then, we introduce actions coordinated by ReDLat and the Latin America and Caribbean Consortium on Dementia (LAC-CD) to develop culturally appropriate diagnostic tools, regional visibility and capacity building, diplomatic coordination in local priority areas, and a knowledge-to-action framework toward a regional action plan. Together, these research and networking initiatives will help to establish strong cross-national bonds, support the implementation of regional dementia plans, enhance health systems’ infrastructure, and increase translational research collaborations across the continent.Item Validación del instrumento Montreal Cognitive Assessment en español en adultos mayores de 60 años(Sociedad Española de Neurología, 2017) Delgado, Iris; Araneda, A; Behrens, María IsabelINTRODUCTION: Few studies have validated the Spanish-language version of the Montreal Cognitive Assessment (MoCA-S) test in Latin American populations. OBJETIVE: To evaluate the psychometric properties and discriminant validity of the MoCA-S in elderly patients in Santiago de Chile. METHODS: 172 individuals were grouped according to their clinical diagnosis based on the Clinical Dementia Rating (CDR) scale as follows: amnestic mild cognitive impairment (aMCI; n±24), non-amnestic MCI (naMCI; n±24), mild dementia (n±20), and cognitively normal (n±104). Participants were evaluated with both the MoCA-S and the Mini-Mental State Examination (MMSE) to determine the discriminant validity of the MoCA-S. RESULTS: Mean age and years of schooling were 73±6 and 11±4 years, respectively, with no significant intergroup differences. The MoCA-S displayed good internal consistency (Cronbach's α: 0.772), high inter-rater reliability (Spearman correlation coefficient: 0.846; P<.01), and high intra-rater reliability (test-retest reliability coefficient: 0.922; P<.001). The MoCA-S was found to be an effective and valid test for detecting aMCI (AUC±0.903) and mild dementia (AUC±0.957); its effectiveness for detecting naMCI was lower (AUC±0.629). The optimal cut-off points for aMCI and mild dementia were<21 and<20, respectively, with sensitivity and specificity rates of 75% and 82% for aMCI and 90% and 86% for mild dementia. The level of education had a great impact on scores: as a result, 2 points were added for patients with less than 8 years of schooling and one point for patients with 8-12 years of schooling (MoCA-S1-2). The MoCA-S1-2 showed significantly greater discriminant validity than the MMSE for differentiating aMCI from dementia. CONCLUSIONS: The MoCA-S1-2 is a short, easy-to-use, and useful test for diagnosing aMCI and mild dementia.