36 research outputs found

    Evaluación de los efectos de un programa de entrenamiento interválico de alta intensidad no específico en tenistas jóvenes de competición

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    El objetivo es comprobar si hay mejora en el rendimiento de un grupo de tenistas de competición adolescentes después de realizar cinco semanas de entrenamientos de hiit no específicos de tenis, y comparar los resultados con un grupo que ha entrenado cinco semanas de entrenamientos hiit especifico en pista de tenis. Para así poder comprobar si ambos entrenamientos son eficaces en el deporte y observar si alguno es más eficaz que el otro

    Perinatal exposure to pesticides alters synaptic plasticity signaling and induces behavioral deficits associated with neurodevelopmental disorders.

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    Increasing evidence from animal and epidemiological studies indicates that perinatal exposure to pesticides cause developmental neurotoxicity and may increase the risk for psychiatric disorders such as autism and intellectual disability. However, the underlying pathogenic mechanisms remain largely elusive. This work was aimed at testing the hypothesis that developmental exposure to different classes of pesticides hijacks intracellular neuronal signaling contributing to synaptic and behavioral alterations associated with neurodevelopmental disorders (NDD). Low concentrations of organochlorine (dieldrin, endosulfan, and chlordane) and organophosphate (chlorpyrifos and its oxon metabolite) pesticides were chronically dosed ex vivo (organotypic rat hippocampal slices) or in vivo (perinatal exposure in rats), and then biochemical, electrophysiological, behavioral, and proteomic studies were performed. All the pesticides tested caused prolonged activation of MAPK/ERK pathway in a concentration-dependent manner. Additionally, some of them impaired metabotropic glutamate receptor-dependent long-term depression (mGluR-LTD). In the case of the pesticide chlordane, the effect was attributed to chronic modulation of MAPK/ERK signaling. These synaptic alterations were reproduced following developmental in vivo exposure to chlordane and chlorpyrifos-oxon, and were also associated with prototypical behavioral phenotypes of NDD, including impaired motor development, increased anxiety, and social and memory deficits. Lastly, proteomic analysis revealed that these pesticides differentially regulate the expression of proteins in the hippocampus with pivotal roles in brain development and synaptic signaling, some of which are associated with NDD. Based on these results, we propose a novel mechanism of synaptic dysfunction, involving chronic overactivation of MAPK and impaired mGluR-LTD, shared by different pesticides which may have important implications for NDD.Open Access funding provided thanks to the CRUE-CSIC agreement with Springer Nature. This work was supported by the Intertalentum Postdoctoral Program (Marie Curie cofund UAM-UE, EU project 713366) for V.B. and by grants from the Spanish Ministry of Science and Innovation (SAF2017-86983-R, PID2020-117651RB) and from the Spanish Ministry of Economy and Competitiveness (PCIN-2016– 095) for J.A.E.. V.B. was also recipient of the 2019 Eduardo Gallego postdoctoral fellowship from Fundación Francisco Cobos. M.I.C. was recipient of a postdoctoral fellowship from the Spanish Ministry of Economy (IJCI-2015–25507). E.LM. was recipient of a predoctoral fellowship from the Spanish Ministry of Science and Innovation (FPU18/02838).S

    Análisis térmico y de potencia de multiprocesadores con DVFS

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    Este trabajo se centra en la caracterización térmica y energética de dos plataformas: Raspberry Pi y la placa base Asus Rampage VI Extreme Omega. Además, se documenta el control de potencia y rendimiento que estas realizan. <br /

    Differential Estrogenic Effects of the Persistent Organochlorine Pesticides Dieldrin, Endosulfan, and Lindane in Primary Neuronal Cultures

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    The organochlorine chemicals endosulfan, dieldrin, and ghexachlorocyclohexane (lindane) are persistent pesticides to which people are exposed mainly via diet. Their antagonism of the g-aminobutyric acid-A (GABAA) receptor makes them convulsants. They are also endocrine disruptors because of their interaction with the estrogen receptor (ER). Here, we study the effects of dieldrin, endosulfan, and lindane on ERs in primary cultures of cortical neurons (CN) and cerebellar granule cells (CGC). All the compounds tested inhibited the binding of [3H]-estradiol to the ER in both CN and CGC, with dieldrin in CGC showing the highest affinity.We also determined the effects of the pesticides on protein kinase B (Akt) and extracellular-regulated kinase 1 and 2 (ERK1/2) phosphorylation. Dieldrin and endosulfan increased Akt phosphorylation in CN, which was inhibited by the ERb antagonist 4-[2-phenyl-5,7- bis(trifluoromethyl)pyrazolo[1,5-a]pyrimidin-3-yl]phenol. Instead, Akt and ERK1/2 phosphorylation induced by dieldrin in CGC was mediated by multiple activation of ERa, ERb, and G protein– coupled receptor 30. Lindane did not activate these pathways, but it inhibited estradiol-mediated Akt and ERK1/2 activation. In CN, all the chemicals activated ERK1/2 through a mechanism involving GABAA and glutamate receptors. Long-term exposure to these pesticides reduced the levels of ERa, but not of ERb. Moreover, extracts of CN treated with endosulfan, dieldrin, or lindane induced cell proliferation in MCF-7 human breast cancer–derived cells, whereas only extracts of CGC treated with dieldrin induced MCF-7 cell proliferation. Overall, the observed alterations on ER-mediated signaling and ER levels in neurons might contribute to the neurotoxicity of these organochlorine pesticides.Ministry of Health(FIS 061212, FIS 10/0453); CIBERESP (AA08-001); Generalitat de Catalunya (2009/SGR/214); Consejerı ´a de Innovacio´n, Ciencia y Empresa de la Junta de Andalucı´a (P09-CTS-5488).Peer reviewe

    Functional specialization of different PI3K isoforms for the control of neuronal architecture, synaptic plasticity, and cognition

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    Neuronal connectivity and activity-dependent synaptic plasticity are fundamental properties that support brain function and cognitive performance. Phosphatidylinositol 3-kinase (PI3K) intracellular signaling controls multiple mechanisms mediating neuronal growth, synaptic structure, and plasticity. However, it is still unclear how these pleiotropic functions are integrated at molecular and cellular levels. To address this issue, we used neuron-specific virally delivered Cre expression to delete either p110α or p110β (the two major catalytic isoforms of type I PI3K) from the hippocampus of adult mice. We found that dendritic and postsynaptic structures are almost exclusively supported by p110α activity, whereas p110β controls neurotransmitter release and metabotropic glutamate receptor–dependent long-term depression at the presynaptic terminal. In addition to these separate functions, p110α and p110β jointly contribute to N-methyl-d-aspartate receptor–dependent postsynaptic long-term potentiation. This molecular and functional specialization is reflected in different proteomes controlled by each isoform and in distinct behavioral alterations for learning/memory and sociability in mice lacking p110α or p110β.This work was supported by the Spanish Ministry of Science and Innovation grants SAF2017-86983-R and PID2020-117651RB (to J.A.E.), Spanish Ministry of Science and Innovation grants SAF2017-89116R-P (FEDER/EU) and PID2020-116184RB (to M.G.), Carlos III Institute of Health-Fondo de Investigación Sanitaria grant PRB3 (IPT17/0019–ISCIII-SGEFI/ERDF, ProteoRed) and CIBERCV (to J.A.L.), Spanish Ministry of Economy postdoctoral contract IJCI-2015-25507 (to M.I.C.), Marie Curie cofund UAM-UE (EU project 713366) Intertalentum Postdoctoral Program (to V.B.), and Spanish Ministry of Science and Innovation predoctoral contracts (to C.S.-C., A.F.-R., and S.L.-G.). The CNIC is supported by the Instituto de Salud Carlos III (ISCIII), the Ministerio de Ciencia e Innovación (MCIN), and the Pro CNIC Foundation, and is a Severo Ochoa Center of Excellence (grant CEX2020-001041-S funded by MICIN/AEI/10.13039/501100011033)

    Control of protein synthesis and memory by GluN3A-NMDA receptors through inhibition of GIT1/mTORC1 assembly

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    De novo protein synthesis is required for synapse modifications underlying stable memory encoding. Yet neurons are highly compartmentalized cells and how protein synthesis can be regulated at the synapse level is unknown. Here, we characterize neuronal signaling complexes formed by the postsynaptic scaffold GIT1, the mechanistic target of rapamycin (mTOR) kinase, and Raptor that couple synaptic stimuli to mTOR-dependent protein synthesis; and identify NMDA receptors containing GluN3A subunits as key negative regulators of GIT1 binding to mTOR. Disruption of GIT1/mTOR complexes by enhancing GluN3A expression or silencing GIT1 inhibits synaptic mTOR activation and restricts the mTOR-dependent translation of specific activity-regulated mRNAs. Conversely, GluN3A removal enables complex formation, potentiates mTOR-dependent protein synthesis, and facilitates the consolidation of associative and spatial memories in mice. The memory enhancement becomes evident with light or spaced training, can be achieved by selectively deleting GluN3A from excitatory neurons during adulthood, and does not compromise other aspects of cognition such as memory flexibility or extinction. Our findings provide mechanistic insight into synaptic translational control and reveal a potentially selective target for cognitive enhancementRamon y Cajal program RYC2014-15784, RETOS-MINECO SAF2016-76565-R, ERANET-Neuron JTC 2019 ISCIII AC19/00077 FEDER funds (to R.A.); RETOS-MINECO SAF2017-87928-R (to A.B.); an NIH grant (NS76637) and UTHSC College of Medicine funds (to S.J.T.); and NARSAD Independent Investigator Award and grants from the MINECO (CSD2008-00005, SAF2013-48983R, SAF2016-80895-R), Generalitat Valenciana (PROMETEO 2019/020)(to I.P.O.) and Severo-Ochoa Excellence Awards (SEV-2013-0317, SEV-2017-0723)Peer reviewe

    Total absorption gamma-ray spectroscopy study of the β-decay of 186Hg

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    7 pags., 9 figs., 1 tab.The Gamow-Teller strength distribution of the decay of Hg into Au has been determined for the first time using the total absorption gamma spectroscopy technique and has been compared with theoretical QRPA calculations using the SLy4 Skyrme force. The measured Gamow-Teller strength distribution and the half-life are described by mixing oblate and prolate configurations independently in the parent and daughter nuclei. In this theoretical framework the best description of the experimental beta strength is obtained with dominantly prolate components for both parent Hg and daughter Au. The approach also allowed us to determine an upper limit of the oblate component in the parent state. The complexity of the analysis required the development of a new approach in the analysis of the X-ray gated total absorption spectrum.This work was supported by Spanish Ministerio de Economía y Competitividad under grants FPA2011-24553, FPA2014-52823-C2-1-P, FPA2017-83946-C2-1-P, FPA2017-87568-P, Ministerio de Ciencia e Innovación grants PID2019-104714GB-C21 and RTI2018-098868-B-100, program Severo Ochoa (SEV-2014-0398), ENSAR (grant 262010) and by the European Union Horizon 2020 research and innovation programme under Grant Agreement No. 654002. S.E.A.O. thanks the support of CPAN Consolider-Ingenio 2010 Programme CSD2007-00042 grant. E.G. acknowledges support from TÜBITAK 2219 Abroad Research Fellowship Programme. R.B.C. acknowledges support by the Max-Planck-Partner group. Support from the technical staff and engineers of ISOLDE-CERN is acknowl- edged. W.G. acknowledges the support of STFC (UK) council grant ST/P005314/1. V.G. acknowledges the support of the National Science Center, Poland, under Contract No. 2019/35/D/ST2/02081. This work was also supported by the National Research, Development and Innovation Fund of Hungary, financed under the K18 funding scheme with Projects No. K 128729 and NN128072. P.S. acknowledges support from MCI/AEI/FEDER, UE (Spain) under grant PGC2018-093636-B-I0

    Homeostatic regulation of glutamate neurotransmission in primary neuronal cultures

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    El pdf es la versión post-print.Glutamate is the mayor excitatory neurotransmitter in vertebrate nervous system. It has a crucial role in most brain functions under physiological conditions through the activation of both ionotropic and metabotropic glutamate receptors. In addition, extracellular glutamate concentration is tightly regulated through different excitatory amino acid transporters (EAAT). Glutamate neurotransmission is also involved in the neurotoxic effects of many environmental chemicals and drugs. Furthermore, homeostatic changes in glutamate neurotransmission appear in response to prolonged block / enhancement of electrical activity. Here we describe different approaches to evaluate alterations in glutamate neurotransmission regarding glutamate receptors and glutamate transporters by using primary cultures of neurons and of astrocytes. The methods are based on the increased fluorescence of calcium-sensitive probes in response to glutamate agonists, on radioligand binding to glutamate receptors and transport sites and on inmunocytochemistry visualization of glutamate receptors.This work was supported by grant PI 06/1212 (Spanish Ministry of Health) and SGR 2009/SGR/214 (Generalitat de Catalunya, Spain).Peer Reviewe

    Efectos de los pesticidas organoclorados sobre la neurotransmisión glutamatérgica en cultivos primarios neuronales. Interacciones con el sistema neuroendocrino

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    Tesis Doctoral presentada por Víctor Briz Herrezuelo para optar al grado de Doctor por la Universidad de Barcelona, programa de doctorando de Biomedicina.-- Tesis realizada en el Departamento de Neuroquímica y Neurofarmacología del IIBB-CSIC, IDIBAPS y CIBERESP.Este trabajo ha sido financiado gracias a una beca predoctoral IDIBAPS, desde febrero de 2007 hasta diciembre de 2010. este trabajo ha sido financiado por los siguientes proyectos: >Identificación de dianas moleculares y funcionales alteradas en procesos de neurotoxicidad inducida por contaminantes ambientales y biocidas en cultivos neuronales> (PI 06/1212). Grupo de Investigación consolidado >Farmacología y Toxicología> (2005/SGR/00826) y (2009/SGR/214). >Neurotoxicidad de agentes ambientales, exposición de la población y salud publica> (CB06/02/0024). >Neuroestrogenicidad de plaguicidas organoclorados> (CIBERESP, AA08-001). >Estudio de mecanismos de neurotoxicidad crónica de contaminantes tóxicos: papel de los receptores GABA-A, de glutamato y de estrógenos. Posibles intervenciones terapeúticas> (PI10/00453).Peer Reviewe
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