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

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

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

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

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

Adición no simbólica en niños preescolares de la Argentina

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

Transcriptional characterization of wnt and notch signaling pathways in neuronal differentiation of human adipose tissue-derived stem cells

Since the nervous system has limited self-repair capability, a great interest in using stem cells is generated to repair it. The adipose tissue is an abundant source of stem cells and previous reports have shown the differentiation of them in neuron-like cells when cultures are enriched with growth factors involved in neurogenesis. Regarding this, it could be thought that a functional parallelismbetween neurogenesis and neuronal differentiation of human adipose stem cells (hASCs) exists. For this reason, we investigated the putative involvement ofNotch and Wnt pathways in neuronal differentiation of hASCs through real-time PCR. We found that both Wnt and Notch signaling are present in proliferating hASCs and that both cascades are downregulated when cells are differentiated to a neuronal phenotype. These results are in concordance with previous works where it was found that both pathways are involved in the maintenance of the proliferative state of stem cells, probably through inhibition of the expression of cell-fatespecific genes. These results could support the notion that hASCs differentiation into neuron-like cells represents a regulated process analogous to what occurs during neuronal differentiation of NSCs and could partially contribute to elucidate 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. Instituto de Ciencias Básicas y Medicina Experimental; ArgentinaFil: Gomez, Daniel Eduardo. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Oncología Molecular; ArgentinaFil: Argibay, Pablo Francisco. Hospital Italiano. Instituto de Ciencias Básicas y Medicina Experimental; Argentin

The computational influence of neurogenesis in the processing of spatial information in the dentate gyrus

This study was designed to analyze the effect of hippocampal neurogenesis on the spatial maps of granule cells. Accordingly, we developed and improved an artificial neural network that was originally proposed by Aimone. Many biological processes were included in this revised model to improve the biological relevance of the results. We proposed a novel learning-testing protocol to analyze the activation of encoding place cells across contexts and over time in the dentate gyrus. We observed that, regardless of the presence of neurogenesis, the quantity and morphology of the place fields were represented in the same manner by granule cells. Additionally, we observed that neurogenesis was an effective mechanism for reducing the degree of rate remapping that occurred in the place fields of the granule cells.Fil: Cuneo, Javier I.. Hospital Italiano. Instituto de Ciencias Básicas y Medicina Experimental; ArgentinaFil: Quiroz, Nicolas H.. Hospital Italiano. Instituto de Ciencias Básicas y Medicina Experimental; ArgentinaFil: 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

Modulation of isoforms of CD44 adhesion molecule in a murine model of gut-ischemia-reperfusion

La isquemia y reperfusión intestinal (I-RI) desencadena un proceso inflamatorio a nivel sistémico, en el cual los leucocitos contribuyen a los efectos deletéreos mas aliá de la pared intestinal. La infiltración leucocitaria de órganos de choque de I-RI como los pulmones y el hígado involucra a las moléculas de adhesión ICAM-1 y CD11/CD18. Se ha destacado la participación de la molécula de adhesión CD44 en otros procesos inflamatorios tales como artritis reumatoidea o dermatitis alérgica de contacto, sin embargo se desconoce su implicancia en la patogenia de I-RI. Con el objetivo de establecer un posible rol de CD44 en el desarrollo de inflamación sistémica por I-RI, hemos estudiado la expresión de esta molécula a nivel del ARNm en un modelo murino de isquemia y reperfusión intestinal. En el hígado y el bazo de animales sometidos a I-RI hallamos un aumento en el número de isoformas variables de CD44 expresadas con respecto a animales no tratados o sometidos a laparotomía. Este hallazgo indica que el proceso de I-RI induce específicamente la expresión de distintas isoformas de CD44. El aumento en la expresión de CD44 observado en el hígado de animales sometidos a I-RI sugiere la.contribución de esta molécula de adhesión a la activación y migración de linfocitos hacia este órgano injuriado. Por otra parte, el incremento en el número de isoformas expresadas en bazo estaría inducido por el microambiente proinflamatorio que resulta de la actividad de depuración sistémica del mismo.Gut ischemia-reperfusion (G-IR) induces a systemic inflammatory response, in which leukocyte contribution to this injury in distant organs is important. ICAM-1 as well as CD11/CD18 have been involved in leukocyte infiltration in liver and lungs. CD44 adhesion molecule plays an essential role in other inflammatory processes such as rheumatoid arthritis and allergic contact dermatitis, however its implication in G-IR has not been described. In order to establish a possible role of CD44 in the development of systemic inflammation by G-IR, we have studied CD44 mANA expression by RT-PCR in a murine model of gut ischemia reperfusion. Animals subjected to G-IR showed an increased number of CD44 variable isoforms expressed in liver and spleen compared to non-treated animals or animals subjected to laparotomy. This finding indicates that G-IA specifically induces the expression of different CD44 variable isoforms. Liver CD44 upregulation in animals subjected to G-IR suggests a contribution of this molecule to Iymphocyte activation and migration to this injured organ. Moreover, increased isoform expression in spleen may be induced by the proinflammatory environment resulting from a systemic depuration activity.Fil: Cabrera, Paula V.. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni; ArgentinaFil: Blanco, Guillermo Armando C.. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni; ArgentinaFil: Argibay, Pablo. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Hospital Italiano; ArgentinaFil: Hajos, Silvia Elvira. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni; Argentin

Google Trends relacionado a la influenza

The recent paper on Using Google Trends (GT) to Estimate the Incidence of Influenza-Like Illness in Argentina 1 is very interesting. Orellano et al. studied Google Flu Trends (GFT) and GT with a conclusion regarding “the utility of GT to complement influenza surveillance”. Indeed, the usefulness of GFT and GT has been mentioned in some earlier reports 2,3. However, as a computational model, there are several things to be considered in the simulation 4. Under- or over-estimation can be expected and this is still the present problem in using the Google system for predicting influenza 4. There is a need for modifications of GT and GFT into a more specific tool that is appropriate for each context. A good example of this is the development of FluBreaks by Pervaiz et al.Fil: Wiwanitkit, Viroj. Wiwanitkit House; Tailandia. Surin Rajabhat University; Tailandia. Hainan Medical College; ChinaFil: Orellano, Pablo Wenceslao. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Surin Rajabhat University; TailandiaFil: Reynoso, Julieta Itati. Wiwanitkit House; TailandiaFil: Antman, Julián. Hainan Medical College; ChinaFil: Argibay, Osvaldo. Hainan Medical College; Chin