761 research outputs found

    Notch/neurogenin 3 signalling is involved in the neuritogenic actions of oestradiol in developing hippocampal neurones

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    10 pages. - PMID: 21251092 [PubMed - in process]The ovarian hormone oestradiol promotes neuritic outgrowth in different neuronal types, by mechanisms that remain elusive. Recent studies have shown that the Notch-regulated transcription factor neurogenin 3 controls neuritogenesis. In the present study, we assessed whether oestradiol regulates neurogenin 3 in primary hippocampal neurones. As expected, neuritogenesis was increased in the cultures treated with oestradiol. However, the neuritogenic action of oestradiol was not prevented by ICI 182,780, an antagonist of classical oestrogen receptors (ERs). Oestradiol decreased the expression of Hairy and Enhancer of Split-1, a Notch-regulated gene that negatively controls the expression on neurogenin 3. Furthermore, oestradiol increased the expression of neurogenin 3 and regulated its distribution between the neuronal cell nucleus and the cytoplasm. The effect of oestradiol on neurogenin 3 expression was not blocked by antagonists of classical nuclear ER-mediated transcription and was not imitated by selective agonists of nuclear ERs. By contrast, G1, a ligand of G protein receptor 30/G protein-coupled ER, fully reproduced the effect of oestradiol on neuritogenesis, neurogenin 3 expression and neurogenin 3 subcellular localisation. Moreover, knockdown of neurogenin 3 in neurones by transfection with small interference RNA for neurogenin 3 completely abrogated the neuritogenic actions of oestradiol and G1. These results suggest that oestradiol regulates neurogenin 3 in primary hippocampal neurones by a nonclassical steroid signalling mechanism, which involves the down-regulation of Notch activity and the activation of G protein receptor 30/G protein-coupled ER or of other unknown G1 targets. In addition, our findings indicate that neurogenin 3 participates in the neuritogenic mechanisms of oestradiol in hippocampal neurones.Peer reviewe

    Role of X-linked genes on sex differences in neurogenin 3 expression in developing hypothalamic neurons

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    Fil: Cisternas, Carla Daniela. Universidad Nacional de Córdoba. Facultad de Odontología. Cátedra de Biología Celular; Argentina.Fil: Cisternas, Carla Daniela. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas, Físicas y Naturales. Cátedra de Fisiología Animal; Argentina.Fil: Cisternas, Carla Daniela. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigación Médica Mercedes y Martín Ferreyra; Argentina.Fil: Arévalo, María Ángeles. Consejo Superior de Investigaciones Científicas; España.Fil: Garcia-Segura, Luis Miguel Consejo Superior de Investigaciones Científicas; España.Fil: Cambiasso, María Julia. Universidad Nacional de Córdoba. Facultad de Odontología. Cátedra de Biología Celular B; Argentina.Fil: Cambiasso, María Julia. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigación Médica Mercedes y Martín Ferreyra; Argentina.Our previous findings indicate that sex chromosome complement regulates the generation of sex differences in mouse hypothalamic neuronal development. Higher expression of neurogenin 3 (Ngn3) in XX neurons mediates sex differences in the rate of neuronal differentiation. Since Ngn3 is located in chromosome 10, these sex differences should be consequence of differences in the expression of X or Y chromosome genes that result from the inherent sex difference in the number (two copies of X) and/or type (presence or absence of Y) of sex chromosomes. We tested the hypothesis that X genes that escape X-inactivation are involved in regulation of sex differences in autosomal expression of Ngn3 and axonal length of hypothalamic neurons. To deal with this aim we evaluated the expression of Ddx3x, Eif2s3x, Kdm5c, Kdm6a, Mid1 and Usp9x in primary neuronal cultures from E14 male and female mice.http://falan-ibrolarc.org/drupal/es/content/scientific-programmeFil: Cisternas, Carla Daniela. Universidad Nacional de Córdoba. Facultad de Odontología. Cátedra de Biología Celular; Argentina.Fil: Cisternas, Carla Daniela. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas, Físicas y Naturales. Cátedra de Fisiología Animal; Argentina.Fil: Cisternas, Carla Daniela. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigación Médica Mercedes y Martín Ferreyra; Argentina.Fil: Arévalo, María Ángeles. Consejo Superior de Investigaciones Científicas; España.Fil: Garcia-Segura, Luis Miguel Consejo Superior de Investigaciones Científicas; España.Fil: Cambiasso, María Julia. Universidad Nacional de Córdoba. Facultad de Odontología. Cátedra de Biología Celular B; Argentina.Fil: Cambiasso, María Julia. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigación Médica Mercedes y Martín Ferreyra; Argentina.Bioquímica y Biología Molecular (ídem 3.1.10

    Role of sex chromosome complement in the regulation of aromatase expression in developing mice brain

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    Fil: Cisternas, Carla Daniela. Universidad Nacional de Córdoba. Facultad de Odontología. Cátedra de Biología Celular; Argentina.Fil: Cisternas, Carla Daniela. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas, Físicas y Naturales. Cátedra de Fisiología Animal; Argentina.Fil: Cisternas, Carla Daniela. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigación Médica Mercedes y Martín Ferreyra; Argentina.Fil: Arévalo, María Ángeles. Consejo Superior de Investigaciones Científicas; España.Fil: Garcia-Segura, Luis Miguel Consejo Superior de Investigaciones Científicas; España.Fil: Cambiasso, María Julia. Universidad Nacional de Córdoba. Facultad de Odontología. Cátedra de Biología Celular B; Argentina.Fil: Cambiasso, María Julia. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigación Médica Mercedes y Martín Ferreyra; Argentina.During the critical period of sexual differentiation there are sex differences in brain aromatase expression that are time and regionally specific. Some of these sex differences cannot be explained by organizational — actions of — gonadal hormones because they occur before exposition to testosterone in — utero. Previous results from our group using the four core genotype mouse model (FCG) demonstrate that XY neurons from amygdala express -higher levels of aromatase and Cyp19al than XX neurons of E15 mice independent of gonadal sex. The present study explores the regulation of aromatase in amygdala neurons from E15 mice brain and the role of estrogen (ERa and ERB) and androgen receptors (AR) in this regulation.https://www.sfn.org/annual-meeting/neuroscience-2016/abstractsFil: Cisternas, Carla Daniela. Universidad Nacional de Córdoba. Facultad de Odontología. Cátedra de Biología Celular; Argentina.Fil: Cisternas, Carla Daniela. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas, Físicas y Naturales. Cátedra de Fisiología Animal; Argentina.Fil: Cisternas, Carla Daniela. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigación Médica Mercedes y Martín Ferreyra; Argentina.Fil: Arévalo, María Ángeles. Consejo Superior de Investigaciones Científicas; España.Fil: Garcia-Segura, Luis Miguel Consejo Superior de Investigaciones Científicas; España.Fil: Cambiasso, María Julia. Universidad Nacional de Córdoba. Facultad de Odontología. Cátedra de Biología Celular B; Argentina.Fil: Cambiasso, María Julia. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigación Médica Mercedes y Martín Ferreyra; Argentina.Bioquímica y Biología Molecular (ídem 3.1.10

    Neurogenin 3 mediates sex chromosome effects on the generation of sex differences in hypothalamic neuronal development.

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    The organizational action of testosterone during critical periods of development is the cause of numer o ussex differences in the brain. However, sex differences in neuritogenesis have been detectedin primary neuronal hypothalamic cultures prepared before the peak of testosterone production by fetal testis. In the present study we assessed the hypothesis of that cell-autonomous action of sex chromosomes can differentially regulate the expression of the neuritogenic gene neurogenin 3 (Ngn3) in male and female hypothalamic neurons, generating sex differences in neuronal development. Neuronal cultures were prepared from male and female E14 mouse hypothalami, before the fetal peak of testosterone. Female neurons showed enhanced neuritogenesis and higher expressionof Ngn3 than maleneurons. The silencing of Ngn3 abolished sex differences in neuritogenesis, decreasing the differentiation off e mal e neurons. The sex difference in Ngn3 expression was determined by sex chromosomes, as demonstrated using the four core genotypes mouse model, in which a spontaneous deletion of the testis-determining gene Sry from the Y chromosome was combined with the insertion of the Sry gene onto an autosome. In addition, the expression of Ngn3, which is also known to mediate the neuritogenic actions of estradiol, was increased in the cultures treated with the hormone, but only in those from male embryos. Furthermore, the hormone reversed the sex difference sin neuritogenesis promoting the differentiation of male neurons. These findings indicate that Ngn3 mediates both cell-autonomous actions of sex chromosomes and hormonal effects on neuritogenesis.publishedVersio

    Estradiol-dependent axogenesis and Ngn3 expression are determined by XY sex chromosome complement in hypothalamic neurons

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    Hypothalamic neurons show sex differences in neuritogenesis, female neurons have longer axons and higher levels of the neuritogenic factor neurogenin 3 (Ngn3) than male neurons in vitro. Moreover, the effect of 17-β-estradiol (E2) on axonal growth and Ngn3 expression is only found in male-derived neurons. To investigate whether sex chromosomes regulate these early sex differences in neuritogenesis by regulating the E2 effect on Ngn3, we evaluated the growth and differentiation of hypothalamic neurons derived from the “four core genotypes” mouse model, in which the factors of “gonadal sex” and “sex chromosome complement” are dissociated. We showed that sex differences in neurite outgrowth are determined by sex chromosome complement (XX > XY). Moreover, E2 increased the mRNA expression of Ngn3 and axonal length only in XY neurons. ERα/β expressions are regulated by sex chromosome complement; however, E2-effect on Ngn3 expression in XY neurons was only fully reproduced by PPT, a specific ligand of ERα, and prevented by MPP, a specific antagonist of ERα. Together our data indicate that sex chromosomes regulate early development of hypothalamic neurons by orchestrating not only sex differences in neuritogenesis, but also regulating the effect of E2 on Ngn3 expression through activation of ERα in hypothalamic neurons.Fil: Cisternas, Carla Daniela. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra. Universidad Nacional de Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra; ArgentinaFil: Cabrera Zapata, Lucas Ezequiel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra. Universidad Nacional de Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra; ArgentinaFil: Mir, Franco Rafael. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra. Universidad Nacional de Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra; ArgentinaFil: Scerbo, María Julia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra. Universidad Nacional de Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra; ArgentinaFil: Arevalo, María Angeles. Instituto de Salud Carlos Iii (isciii); EspañaFil: García-Segura, Luis Miguel. Instituto de Salud Carlos Iii (isciii); EspañaFil: Cambiasso, Maria Julia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra. Universidad Nacional de Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra; Argentin

    Estradiol Meets Notch Signaling in Developing Neurons

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    The transmembrane receptor Notch, a master developmental regulator, controls gliogenesis, neurogenesis, and neurite development in the nervous system. Estradiol, acting as a hormonal signal or as a neurosteroid, also regulates these developmental processes. Here we review recent evidence indicating that estradiol and Notch signaling interact in developing hippocampal neurons by a mechanism involving the putative membrane receptor G protein-coupled receptor 30. This interaction is relevant for the control of neuronal differentiation, since the downregulation of Notch signaling by estradiol results in the upregulation of neurogenin 3, which in turn promotes dendritogenesis

    FACTORES QUE AFECTAN EL INTERVALO PARTO-PRIMERSERVICIO YPRIMER SERVICIO-CONCEPCIÓN EN VACAS LECHERAS DEL VALLE DELMANTARO DURANTE LAÉPOCALLUVIOSA

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    Se realizó un seguimiento reproductivo en 40 vacas lecheras del valle delMantaro (Junín, Perú), pertenecientes a 6 establos, durante la época lluviosa. Se determinó el intervalo parto-primera ovulación (IPPO), el intervalo parto-primer servicio (IPPS), y el intervalo parto-concepción (IPC), midiendo el efecto de raza, número de parto, producción de leche, establo y nivel tecnológico. El IPPO se determinó a través de niveles de progesterona mediante radioinmunoensayo en muestras de leche descremada. El intervalo observado entre el parto y la primera ovulación (41.2 ± 20.2 días) estuvo dentro de los rangos esperados para bovinos de producción de leche criados bajo las condiciones del presente estudio. Sin embargo, los intervalos entre el parto al primer servicio (118.4 ± 69.2) y a la concepción (171.3 ± 105.5 días) fueronmuy prolongados, debido posiblemente a problemas en la detección del celo y limitantes nutricionales. El nivel tecnológico de los establos fue la única variable de importancia que afectó el intervalo parto-primer servicio.A reproductive study was conducted in the El Mantaro valley, Junín, Peru. Forty milking cows from 6 farms were monitored during the rainy season. The effect of breed, parity, milk yield, farm, and technological level on the interval fromcalving to first ovulation (CFOI), to first service (CFSI), and to conception (CCI) were evaluated. CFOI was determined through progesterone radioimmunoassayconcentration in defatted milk.CFOI was within the expected range for dairy cattle (41.2 ± 20.2 days); however, CFSI (118.4 ± 69.2) and CCI (171.3 ± 105.5 days) were too long, possibly due to heat detection failures and nutritional constraints. Farm technological level was the only variable of importance that affected CFSI

    X-linked histone H3K27 demethylase Kdm6a regulates sexually dimorphic differentiation of hypothalamic neurons

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    Several X-linked genes are involved in neuronal differentiation and may contribute to the generation of sex dimorphisms in the brain. Previous results showed that XX hypothalamic neurons grow faster, have longer axons, and exhibit higher expression of the neuritogenic gene neurogenin 3 (Ngn3) than XY before perinatal masculinization. Here we evaluated the participation of candidate X-linked genes in the development of these sex differences, focusing mainly on Kdm6a, a gene encoding for an H3K27 demethylase with functions controlling gene expression genome-wide. We established hypothalamic neuronal cultures from wild-type or transgenic Four Core Genotypes mice, a model that allows evaluating the effect of sex chromosomes independently of gonadal type. X-linked genes Kdm6a, Eif2s3x and Ddx3x showed higher expression in XX compared to XY neurons, regardless of gonadal sex. Moreover, Kdm6a expression pattern with higher mRNA levels in XX than XY did not change with age at E14, P0, and P60 in hypothalamus or under 17β-estradiol treatment in culture. Kdm6a pharmacological blockade by GSK-J4 reduced axonal length only in female neurons and decreased the expression of neuritogenic genes Neurod1, Neurod2 and Cdk5r1 in both sexes equally, while a sex-specific effect was observed in Ngn3. Finally, Kdm6a downregulation using siRNA reduced axonal length and Ngn3 expression only in female neurons, abolishing the sex differences observed in control conditions. Altogether, these results point to Kdm6a as a key mediator of the higher axogenesis and Ngn3 expression observed in XX neurons before the critical period of brain masculinization.Fil: Cabrera Zapata, Lucas Ezequiel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra. Universidad Nacional de Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra; ArgentinaFil: Cisternas, Carla Daniela. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra. Universidad Nacional de Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra; Argentina. Universidad Nacional de Cordoba. Facultad de Odontologia. Departamento de Biologia Bucal; ArgentinaFil: Sosa, Camila. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra. Universidad Nacional de Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra; ArgentinaFil: Garcia Segura, Luis Miguel. Ciberfes Instituto de Salud Carlos Iii; España. Instituto Cajal; EspañaFil: Arevalo, Maria Angeles. Ciberfes Instituto de Salud Carlos Iii; España. Instituto Cajal; EspañaFil: Cambiasso, Maria Julia. Universidad Nacional de Cordoba. Facultad de Odontologia. Departamento de Biologia Bucal; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra. Universidad Nacional de Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra; Argentin
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