1,720,994 research outputs found

    A putative role for neurogenesis in neurocomputational terms: Inferences from a hippocampal model

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    New neurons are generated daily in the hippocampus during adult life. They are integrated into the existing neuronal circuits according to several factors such as age, physical exercise and hormonal status. At present, the role of these new neurons is debated. Computational simulations of hippocampal function allow the effects of neurogenesis to be explored, at least from a computational perspective. The present work implements a model of neurogenesis in the hippocampus with artificial neural networks, based on a standard theoretical model of biologically plausible hippocampal circuits. The performance of the model in retrieval of a variable number of patterns or memories was evaluated (episodic memory evaluation). The model increased, in a phase subsequent to initial learning, the number of granular cells by 30% relative to their initial number. In contrast to a model without neurogenesis, the retrieval of recent memories was very significantly improved, although remotes memories were only slightly affected by neurogenesis. This increase in the quality of retrieval of new memories represents a clear advantage that we attribute to the neurogenesis process. This advantage becomes more significant for higher storage loads. The model presented here suggests an important functional role of neurogenesis on learning and memory.Fil: Weisz, Victoria I.. Hospital Italiano. Instituto de Ciencias Básicas y Medicina Experimental; ArgentinaFil: Argibay, Pablo. Hospital Italiano. Instituto Universitario. Escuela de Medicina; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin

    Depression and neuroplasticity: Interaction of nervous, endocrine and immune systems

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    La depresión clínica es una enfermedad física y psíquica que presenta bases neuropatológicas, sin embargo aún no se tiene un conocimiento exacto del origen o causas de esta enfermedad. Se conoce que existe un componente genético, aunque el componente ambiental en el desarrollo de la depresión es innegable. El estrés juega un rol esencial en el desencadenamiento de la depresión. La interacción y respuesta del sistema endocrino, inmune y nervioso se encuentran afectadas en este desorden. La observación de los efectos de los antidepresivos sobre la neurotransmisión monoaminérgica ha llevado hace muchos años a la hipótesis de las monoaminas de la depresión. Sin embargo, esta hipótesis ya no puede explicar muchos de los efectos de las drogas antidepresivas. La nueva hipótesis para explicar los efectos de los antidepresivos es la de neuroplasticidad neuronal. Esta hipótesis propone que los cambios que esas drogas producen sobre diversos sistemas, entre ellos el sistema nervioso, el inmune y el endocrino, son capaces de inducir cambios neuroadaptativos en el cerebro. La neuroplasticidad ha sido definida como la habilidad del cerebro para reorganizarse a sí mismo y formar nuevas conexiones neuronales a lo largo de la vida. Se propone que el mecanismo por el cual los antidepresivos logran sus efectos es mediante la neuroplasticidad.Clinical depression is a physical and psychic disease that has neuropathological basis, although the clear understanding of its ethiopathology is still missing. There is evidence of a genetic component in depression, however, the participation of environment is crucial. Stress plays an essential role in the onset of depression. The interaction and the response of the endocrine system with the immune and nervous system are altered in depression. The observation of the effect of antidepressants on monoaminergic transmitters leads to the hypothesis of monoamines. However this hypothesis cannot explain many of the mechanisms involved in the action of antidepressants. The new hypothesis proposed to explain the action of antidepressant is the neuroplasticity hypothesis. This hypothesis suggests that the effects of antidepressants on nervous, immune and endocrine systems are able to induce neuroadaptative changes in the brain. The neuroplasticity have been described as the ability of the brain to reorganize itself and form new neuronal connections throughout life. It is proposed that antidepressants influence neuroplasticity inducing improvements in the symptoms of this illness.Fil: Cassano, Paola Mariana. 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: Argibay, Pablo. 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

    Hepatic cell transplantation in childhood: State of the art

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    En la actualidad, los niños que padecen insuficiencia hepática podrían beneficiarse de un método no convencional de reemplazo funcional, alternativo al trasplante hepático. El deterioro y muerte de los pacientes en lista de espera, impulsan la búsqueda de alternativas en el ámbito del trasplante. El trasplante de células hepáticas se ha constituido en un potencial recurso cuya validación como alternativa o puente al trasplante hepático seguramente resultaría en una sustancial mejoría tanto en la calidad de vida como en la supervivencia de los pacientes. En la presente revisión nos proponemos describir el estado del arte en trasplante de hepatocitos en pediatría.To date, children who suffer from a certain type of illness such as hepatic failure, could benefit with a non conventional functional replacement as an alternative to liver transplantation. Deterioration and death of patients on waiting list encourage the search for alternatives methods within transplantation. Liver cell transplantation has become a potential alternative treatment whose validation as an alternative or as a bridge until the donor appears, will probably contribute to improve the quality of life and survival of the patients. The aim of this review is to describe the state of the art of hepatocyte transplantation in pediatric patients.Fil: Bologna, Anselmo Adrian. Hospital Italiano. Instituto de Ciencias Básicas y Medicina Experimental; ArgentinaFil: Barbich, Mariana. Hospital Italiano. Instituto de Ciencias Básicas y Medicina Experimental; ArgentinaFil: D'Agostino, Daniel. Hospital Italiano; ArgentinaFil: Argibay, Pablo. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Hospital Italiano. Instituto de Ciencias Básicas y Medicina Experimental; Argentin

    Hepatic cell transplantation in childhood: State of the art

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    En la actualidad, los niños que padecen insuficiencia hepática podrían beneficiarse de un método no convencional de reemplazo funcional, alternativo al trasplante hepático. El deterioro y muerte de los pacientes en lista de espera, impulsan la búsqueda de alternativas en el ámbito del trasplante. El trasplante de células hepáticas se ha constituido en un potencial recurso cuya validación como alternativa o puente al trasplante hepático seguramente resultaría en una sustancial mejoría tanto en la calidad de vida como en la supervivencia de los pacientes. En la presente revisión nos proponemos describir el estado del arte en trasplante de hepatocitos en pediatría.To date, children who suffer from a certain type of illness such as hepatic failure, could benefit with a non conventional functional replacement as an alternative to liver transplantation. Deterioration and death of patients on waiting list encourage the search for alternatives methods within transplantation. Liver cell transplantation has become a potential alternative treatment whose validation as an alternative or as a bridge until the donor appears, will probably contribute to improve the quality of life and survival of the patients. The aim of this review is to describe the state of the art of hepatocyte transplantation in pediatric patients.Fil: Bologna, Anselmo Adrian. Hospital Italiano. Instituto de Ciencias Básicas y Medicina Experimental; ArgentinaFil: Barbich, Mariana. Hospital Italiano. Instituto de Ciencias Básicas y Medicina Experimental; ArgentinaFil: D'Agostino, Daniel. Hospital Italiano; ArgentinaFil: Argibay, Pablo. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Hospital Italiano. Instituto de Ciencias Básicas y Medicina Experimental; Argentin

    Adición no simbólica en niños preescolares de la Argentina

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    Introduction. Children take years to learn symbolic arithmetic. Nevertheless, such as animals and human adults, infants and children can represent approximate number in arrays of objects and sequences of events, and use these capacities to perform approximate addition and subtraction. Objective. To evaluate whether preschool children without formal education could perform non-symbolic additions, through abstract representations. Methods. We evaluated 17 preschoolers from a private kindergarten recruited from the city of Buenos Aires. They had to add to groups of blue dots, and then compare their addition with a third group of red dots, determining if the blue or the red dots were more numerous. We measured accuracy of responses of each child. Results. Across all the problems, children performed well above chance (67.89%, chance= 50%, t(16)= 6.89, p <0.001), showing the characteristic ratio effect [F(1, 16)= 8.45, p <0.01, ANOVA], and without resort to non-arithmetic strategies. Conclusions. This study provides further evidence regarding the non-symbolic arithmetic skill present before formal education, and together with recent research, raises important contributions in education, trying to understand how children learn mathematics and to establish new methods of teaching.Introducción. Se requieren muchos años para que los niños aprendan aritmética simbólica. Sin embargo, al igual que los animales y los adultos sin educación formal, los infantes y niños pueden representar el número aproximado de conjuntos de objetos y secuencias de eventos, y utilizar esta capacidad para realizar adiciones y sustracciones aproximadas. Objetivo. Evaluar si niños preescolares que no hayan recibido educación formal son capaces de realizar adiciones no simbólicas a través de representaciones abstractas de la magnitud. Métodos. Los participantes fueron 17 niños preescolares de un jardín de infantes privado de una población de clase media de la Ciudad Autónoma de Buenos Aires. La tarea fue adicionar dos conjuntos de puntos azules presentados por separado y comparar su suma con un conjunto de puntos rojos, determinando si la suma de puntos azules o el conjunto de puntos rojos era más numeroso. Se midió el porcentaje de respuestas correctas de cada niño. Resultados. Los niños respondieron sobre la chance (67,89%, chance= 50%, t(16)= 6,89, p <0,001), observándose el característico efecto de la proporción [(F(1,16)= 8,45, p <0,01, ANOVA] y sin recurrir al uso de estrategias alternativas no aritméticas. Conclusiones. Este trabajo aporta más evidencia sobre las habilidades aritméticas no simbólicas presentes antes de la instrucción formal y genera junto con investigaciones recientes, importantes aportes en el ámbito educativo, que ayudan a entender cómo los niños aprenden matemáticas, un hecho útil para establecer nuevas formas de enseñanza.Fil: Martínez, Julia. Hospital Italiano. Instituto de Ciencias Básicas y Medicina Experimental; ArgentinaFil: Argibay, Pablo. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Hospital Italiano. Instituto de Ciencias Básicas y Medicina Experimental; Argentin

    Episodic-like memory: New perspectives from a behavioral test in rats

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    In order to have a tool to empirically test the ideas derived from a theoretical model, we extended a protocol for evaluation of episodic-like memory in rats, based on the triad "what, where, context" for definition of memories. As with the computational model, our intention was for the animal being tested to store a specific number of object-place-context configurations as different memories, which would then be retrievable from cues. The aim of this work was to evaluate the influence of the number of configurations to be memorized on the performance of the task. Sixty-five Wistar male rats were evaluated. In accordance with previous work, for two configurations, the recognition index was indicative of recognition of the element mismatching the original memory (mean = 0.28; SEM = 0.12). The recognition index for three configurations was lower (mean = 0.15; SEM = 0.10), evidencing less recall with increasing requirements. The results also showed a trend toward recognition of novelty for the first and the last memory when evaluating three configurations (a "U" shape in the exploratory preference's curve), showing the primacy and recency effects typical of memory both in humans and animals. Nonetheless, the data presented a high inter-subject variability which makes the test non-robust for small groups. However, if used before and after a treatment for a same subject, we suggest that the protocol presented in this work can be a useful behavioral test for the evaluation of episodic-like memory in rats in terms of a variable task demand.Fil: Weisz, Victoria I.. Hospital Italiano. Instituto de Ciencias Básicas y Medicina Experimental; ArgentinaFil: Rios, Mariana B.. Hospital Italiano. Instituto de Ciencias Básicas y Medicina Experimental; ArgentinaFil: Argibay, Pablo. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Hospital Italiano. Instituto de Ciencias Básicas y Medicina Experimental; Argentin

    Neurogenic differentiation of human adipose-derived stem cells: Relevance of different signaling molecules, transcription factors, and key marker genes

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    Since numerous diseases affect the central nervous system and it has limited self-repair capability, a great interest in using stem cells as an alternative cell source is generated. Previous reports have shown the differentiation of adipose-derived stem cells in neuron-like cells and it has also been proved that the expression pattern of patterning, proneural, and neural factors, such as Pax6, Mash1, Ngn2, NeuroD1, Tbr2 and Tbr1, regulates and defines adult neurogenesis. Regarding this, we hypothesize that a functional parallelism between adult neurogenesis and neuronal differentiation of human adipose-derived stem cells exists. In this study we differentiate human adipose-derived stem cells into neuron-like cells and analyze the expression pattern of different patterning, proneural, neural and neurotransmitter genes, before and after neuronal differentiation. The neuron-like cells expressed neuronal markers, patterning and proneural factors characteristics of intermediate stages of neuronal differentiation. Thus we demonstrated that it is possible to differentiate adipose-derived stem cells in vitro into immature neuron-like cells and that this process is regulated in a similar way to adult neurogenesis. This may contribute to elucidate molecular mechanisms involved in neuronal differentiation of adult human non-neural cells, in aid of the development of potential therapeutic tools for diseases of the nervous system.Fil: Cardozo, Alejandra Johana. Hospital Italiano; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Gomez, Daniel Eduardo. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Oncología Molecular; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Argibay, Pablo. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Hospital Italiano; Argentin

    Elevated Hippocampal Cholinergic Neurostimulating Peptide precursor protein (HCNP-pp) mRNA in the amygdala in major depression

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    The amygdala is innervated by the cholinergic system and is involved in major depressive disorder (MDD). Evidence suggests a hyper-activate cholinergic system in MDD. Hippocampal Cholinergic Neurostimulating Peptide (HCNP) regulates acetylcholine synthesis. The aim of the present work was to investigate expression levels of HCNP-precursor protein (HCNP-pp) mRNA and other cholinergic-related genes in the postmortem amygdala of MDD patients and matched controls (females: N=16 pairs; males: N=12 pairs), and in the mouse unpredictable chronic mild stress (UCMS) model that induced elevated anxiety-/depressive-like behaviors (females: N=6 pairs; males: N=6 pairs). Results indicate an up-regulation of HCNP-pp mRNA in the amygdala of women with MDD (p<0.0001), but not males, and of UCMS-exposed mice (males and females; p=0.037). HCNP-pp protein levels were investigated in the human female cohort, but no difference was found. There were no differences in gene expression of acetylcholinesterase (AChE), muscarinic (mAChRs) or nicotinic receptors (nAChRs) between MDD subjects and controls or UCMS and control mice, except for an up-regulation of AChE in UCMS-exposed mice (males and females; p=0.044). Exploratory analyses revealed a baseline expression difference of cholinergic signaling-related genes between women and men (p<0.0001). In conclusion, elevated amygdala HCNP-pp expression may contribute to mechanisms of MDD in women, potentially independently from regulating the cholinergic system. The differential expression of genes between women and men could also contribute to the increased vulnerability of females to develop MDD.Fil: Bassi, Sabrina Cecilia. University of Pittsburgh; Estados Unidos. Hospital Italiano. Instituto de Ciencias Básicas y Medicina Experimental; ArgentinaFil: Seney, Marianne L.. University of Pittsburgh; Estados UnidosFil: Argibay, Pablo. Hospital Italiano. Instituto de Ciencias Básicas y Medicina Experimental; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Sibille, Etienne. University of Pittsburgh; Estados Unidos. University of Toronto; Canad

    Differential expression of Shh and BMP signaling in the potential conversion of human adipose tissue stem cells into neuron-like cells in vitro

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    The nervous system (NS) has a limited self-repair capability and adult neurogenesis is limited to certain regions of the brain. This generates a great interest in using stem cells to repair the NS. Previous reports have shown the differentiation of adipose tissue-derived mesenchymal stem cells (ASCs) in neuron-like cells when cultures are enriched with growth factors participating in embryonic and adult neurogenesis. Therefore, it could be thought that there exists a functional parallelism between neurogenesis and neuronal differentiation of ASCs. For this reason, the goal of this work was to study the differential gene expression of Shh and BMP genetic pathways involved in cell fate determination and proliferation. In this study we demonstrated that hASCs are endowed with active Hedgehog and BMP signaling pathways through the expression of genes of both cascades and that their expressions are downregulated after neuronal induction. This idea is in accordance with the facts that Shh and BMP signaling is involved in the maintenance of cells with stem cells properties and that proliferation decreases during the process of differentiation. Furthermore, Noggin expression was detected in induced hASCs whereas there was no expression in noninduced cells, which indicates that these cells are probably adopting a neuronal fate because noggin diverts neural stem cells from glial to neuronal fate. We also detected FM1-43 and synaptophisin staining, which is evidence of the presence of putative functional presynaptic terminals, a neuron-specific property. These results could partially contribute to the elucidation of the molecular mechanisms involved in neuronal differentiation of adult human nonneural tissues.Fil: Cardozo, Alejandra Johana. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Hospital Italiano; ArgentinaFil: Ielpi, Marcelo. Hospital Italiano; ArgentinaFil: Gomez, Daniel Eduardo. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología; ArgentinaFil: Argibay, Pablo. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Hospital Italiano; Argentin
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