32 research outputs found

    Human and animal models for translational research on neurodegeneration: Challenges and opportunities from South America

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    Facing the alarming growth of dementia and neurodegenerative conditions has become a critical priority across the globe (Alzheimer´s Disease International, 2009;Lancet, 2015;Shah et al., 2016;Parra et al., 2018). Neurodegenerative diseases are the most frequent cause of dementia, representing a burden for public health systems (especially in middle and middle-high income countries). Although most research on this subject is concentrated in first-world centers, growing efforts in South American countries (SACs) are affording important breakthroughs. This emerging agenda poses not only new challenges for the region, but also new opportunities for the field at large. SACs have witnessed a promising development of relevant research in humans and animals, giving rise to new regional challenges. As highlighted in a recent experts? consensus paper Latin-American countries (LAC), and SACs in particular (Parra et al., 2018), face a critical situation. Higher demographic rates and the predicted prevalence of dementia have reached and even exceeded those of developing countries. In SACs, low- and middle-income countries (e.g., Bolivia, Paraguay), the prevalence of dementia will double that of high-income countries, while upper-middle-income countries in the region (e.g., Argentina, Brazil, Chile, Colombia, Peru, Uruguay, and Venezuela) will experience the greatest impact of dementia. The WHO estimated that the standardized prevalence of dementia in Latin America was 8.5%, but multiple SACs have been underrepresented or underestimated in such a calculation (Parra et al., 2018). Moreover, raw prevalence rates across studies are characterized by high variability within and between countries (e.g., Argentina: 8.3; Brazil: 7.1-2.0; Chile: 4.4-7.0; Colombia: 6.0; Peru: 6.72-9.3; Uruguay: 3.1; Venezuela: 5.7-13,7) (Parra et al., 2018). In addition, most of these studies are undermined by various limitations and methodological problems. Even considering these data, SACs possess the highest global prevalence of dementia after North Africa/Middle East in people above the age of 60 (Parra et al., 2018). Moreover, the harmonization of global strategies against dementia in these contexts is hindered not only by reduced epidemiological data, but also by the lack of standardized clinical practice, insufficient training of physicians, limited resources, and poor governmental support, let alone poverty and more general cultural barriers and stigmas. All of these factors have impacted the type and amount of research conducted in SACs. A regional network, based on multiinstitutional actors from research, governmental, and private sectors is fundamental to overcome these challenges (Parra et al., 2018).Fil: Ibanez Barassi, Agustin Mariano. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Neurociencia Cognitiva. Fundación Favaloro. Instituto de Neurociencia Cognitiva; Argentina. Instituto de Neurología Cognitiva. Laboratorio de Psicología Experimental y Neurociencia; Argentina. Universidad Autónoma del Caribe; Colombia. Universidad Adolfo Ibañez; ChileFil: Sedeño, Lucas. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Neurociencia Cognitiva. Fundación Favaloro. Instituto de Neurociencia Cognitiva; Argentina. Instituto de Neurología Cognitiva. Laboratorio de Psicología Experimental y Neurociencia; ArgentinaFil: García, Adolfo Martín. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Neurociencia Cognitiva. Fundación Favaloro. Instituto de Neurociencia Cognitiva; Argentina. Instituto de Neurología Cognitiva. Laboratorio de Psicología Experimental y Neurociencia; Argentina. Universidad Nacional de Cuyo. Facultad de Educación Elemental y Especial; ArgentinaFil: Deacon, Robert. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Neurociencia Cognitiva. Fundación Favaloro. Instituto de Neurociencia Cognitiva; Argentina. Instituto de Neurología Cognitiva. Laboratorio de Psicología Experimental y Neurociencia; Argentina. Universidad de Chile; ChileFil: Cogram, Patricia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Neurociencia Cognitiva. Fundación Favaloro. Instituto de Neurociencia Cognitiva; Argentina. Instituto de Neurología Cognitiva. Laboratorio de Psicología Experimental y Neurociencia; Argentina. Universidad de Chile; Chil

    Spatial maps and oscillations in the healthy hippocampus of Octodon degus, a natural model of sporadic Alzheimer’s disease

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    The Octodon degus is a South American rodent that is receiving increased attention as a potential model of aging and sporadic late-onset Alzheimer’s disease (AD). Impairments in spatial memory tasks in Octodon degus have been reported in relation to either advanced AD-like disease or hippocampal lesion, opening the way to investigate how the function of hippocampal networks affects behavior across AD stages. However, no characterization of hippocampal electrophysiology exists in this species. Here we describe in young, healthy specimens the activity of neurons and local field potential rhythms during spatial navigation tasks with and without objects. Our findings show similarities between the Octodon degus and laboratory rodents. First, place cells with characteristics similar to those found in rats and mice exist in the CA1 subfield of the Octodon degus. Second, the introduction of objects elicits novelty-related exploration and an increase in activity of CA1 cells, with location specific and unspecific components. Third, oscillations of the local field potential are organized according to their spectral content into bands similar to those found in laboratory rodents. These results suggest a common framework of underlying mechanisms, opening the way to future studies of hippocampal dysfunction in this species associated to aging and disease.Fil: Mugnaini, Matías. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: Polania, Diana. Universidad de Chile; ChileFil: Díaz, Yannina Constanza. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: Ezquer, Marcelo. Universidad del Desarrollo; ChileFil: Ezquer, Fernando. Universidad del Desarrollo; ChileFil: Deacon, Robert M. J.. Universidad de Chile; ChileFil: Cogram, Patricia. Universidad de Chile; Chile. University of California at Irvine; Estados UnidosFil: Kropff, Emilio. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentin

    Dementia in Latin America:Assessing the present and envisioning the future

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    The demographic structure of Latin American countries (LAC) is fast approaching that of developing countries, and the predicted prevalence of dementia in the former already exceeds the latter. Dementia has been declared a global challenge, yet regions around the world show differences in both the nature and magnitude of such a challenge. This article provides evidence and insights on barriers which, if overcome, would enable the harmonization of strategies to tackle the dementia challenge in LAC. First, we analyze the lack of available epidemiologic data, the need for standardizing clinical practice and improving physician training, and the existing barriers regarding resources, culture, and stigmas. We discuss how these are preventing timely care and research. Regarding specific health actions, most LAC have minimal mental health facilities and do not have specific mental health policies or budgets specific to dementia. In addition, local regulations may need to consider the regional context when developing treatment and prevention strategies. The support needed nationally and internationally to enable a smooth and timely transition of LAC to a position that integrates global strategies is highlighted. We focus on shared issues of poverty, cultural barriers, and socioeconomic vulnerability. We identify avenues for collaboration aimed to study unique populations, improve valid assessment methods, and generate opportunities for translational research, thus establishing a regional network. The issues identified here point to future specific actions aimed at tackling the dementia challenge in LAC.Alzheimer's Society UK grants AS-R42303 AS-SF-14-008 CONICYT-Fondecyt 117001

    Dementia in Latin America : paving the way towards a regional action plan

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    Regional challenges faced by Latin American and Caribbean countries (LACs) to fight dementia, such as heterogeneity, diversity, political instabilities, and socioeconomic disparities, can be addressed more effectively grounded in a collaborative setting based on the open exchange of knowledge. In this work, the Latin American and Caribbean Consortium on Dementia (LAC-CD) proposes an agenda for integration to deliver a Knowledge to Action Framework (KtAF). First, we summarize evidence-based strategies (epidemiology, genetics, biomarkers, clinical trials, nonpharmacological interventions, networking and translational research) and align them to current global strategies to translate regional knowledge into actions with transformative power. Then, by characterizing genetic isolates, admixture in populations, environmental factors, and barriers to effective interventions and mapping these to the above challenges, we provide the basic mosaics of knowledge that will pave the way towards a KtAF. We describe strategies supporting the knowledge creation stage that underpins the translational impact of KtAF

    Inositol and protein kinase C in the preventation of neural tube defects

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    Sonic hedgehog and the molecular regulation of mouse neural tube closure

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    Neural tube closure is a fundamental embryonic event whose molecular regulation is poorly understood. As mouse neurulation progresses along the spinal axis, there is a shift from midline neural plate bending to dorsolateral bending. Here, we show that midline bending is not essential for spinal closure since, in its absence, the neural tube can close by a 'default' mechanism involving dorsolateral bending, even at upper spinal levels. Midline and dorsolateral bending are regulated by mutually antagonistic signals from the notochord and surface ectoderm. Notochordal signaling induces midline bending and simultaneously inhibits dorsolateral bending. Sonic hedgehog is both necessary and sufficient to inhibit dorsolateral bending, but is neither necessary nor sufficient to induce midline bending, which seems likely to be regulated by another notochordal factor. Attachment of surface ectoderm cells to the neural plate is required for dorsolateral bending, which ensures neural tube closure in the absence of sonic hedgehog signaling.This work was supported by the Wellcome Trust and the Child Health Research Appeal Trust.Peer reviewe

    How the forebrain transitions to adulthood: developmental plasticity markers in a long-lived rodent reveal region diversity and the uniqueness of adolescence

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    Maturation of the forebrain involves transitions from higher to lower levels of synaptic plasticity. The timecourse of these changes likely differs between regions, with the stabilization of some networks scaffolding the development of others. To gain better insight into neuroplasticity changes associated with maturation to adulthood, we examined the distribution of two molecular markers for developmental plasticity. We conducted the examination on male and female degus (Octodon degus), a rodent species with a relatively long developmental timecourse that offers a promising model for studying both development and age-related neuropathology. Immunofluorescent staining was used to measure perineuronal nets (PNNs), an extracellular matrix structure that emerges during the closure of critical plasticity periods, as well as microglia, resident immune cells that play a crucial role in synapse remodeling during development. PNNs (putatively restricting plasticity) were found to be higher in non-juvenile (>3 month) degus, while levels of microglia (putatively mediating plasticity) decreased across ages more gradually, and with varying timecourses between regions. Degus also showed notable variation in PNN levels between cortical layers and hippocampal subdivisions that have not been previously reported in other species. These results offer a glimpse into neuroplasticity changes occurring during degu maturation and highlight adolescence as a unique phase of neuroplasticity, in which PNNs have been established but microglia remain relatively high

    From genes to cognition: Octodon degus, an animal model for AD translational research

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    Background: Octodon degus (O. degus), a long-lived rodent, provides us with a unique opportunity to search for molecular pathways that are associated with enhanced longevity in mammals. This rodent from Chile spontaneously develops an analog of sporadic AD at behavioral and neurobiological levels. It is a diurnal rodent that makes wide use of spatial memory to find and hide food. This cognitive ability is thought to be rooted in what is commonly known as the GPS of the mammalian brain, a collection of structures centred around the hippocampus and neighbouring cortical areas. A fraction of the aged O. degus population not only exhibits amyloid-beta oligomers, tau hyperphosphorylation, neurofibrillary tangle formation, cell death and cognitive decline but also several other conditions comorbid to AD like diabetes mellitus type 2, macular and retinal degeneration and atherosclerosis. Method: In this study, we used the Octodon degus. Behavioural assessment of a population (N = 150) of degu was performed using the tests of daily living (burrowing test, marble burying and nesting), Novel Object Recognition and the Open Field. All Degus were chronically implanted with a four-tetrode microdrive, which was originally developed for mice (Versadrive-4, Neuralynx, USA). Result: These model features call for research efforts to be put on studying the degu GPS from both the basic and applied science perspectives, with a multilaboratory and multidisciplinary perspective. In response to this, we here present the first multidisciplinary study including i) Recording 69 CA1 principal cells while O. degus explored a 1 m wide square environment, finding that O. degus exhibited extreme place cell behaviour. ii)We performed a genome-wide association study in O. degus and report the identification of SNVs in genes associated with AD (APP, BACE1, MAPT, Psen1 and Psen2, grn and SORL1. iii) Some of the variants identified in AD associated genes showed significant association with behavioural performance in Hardy-Weinberg equilibrium. Conclusion: All together these findings provide an important path toward the understanding how AD related mutations in the O. degus prove this model to be an important translational tool for aging and Alzheimer’s research.Fil: Mugnaini, Matías. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: Deacon, Robert. Universidad de Chile; ChileFil: Sampieri, Guido. Teesside University; Reino UnidoFil: Vanderklish, Peter. The Scripps Research Institute; Estados UnidosFil: Angione, Claudio. Teesside University; Reino UnidoFil: Kropff, Emilio. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: Cogram, Patricia. No especifíca
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