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  • The vasopressin V1b receptor critically regulates hypothalamic-pituitary-adrenal axis activity under both stress and resting conditions. 14722621

    The neurohypophyseal peptide [Arg(8)]-vasopressin (AVP) exerts major physiological actions through three distinct receptor isoforms designated V1a, V1b, and V2. Among these three subtypes, the vasopressin V1b receptor is specifically expressed in pituitary corticotrophs and mediates the stimulatory effect of vasopressin on ACTH release. To investigate the functional roles of V1b receptor subtypes in vivo, gene targeting was used to create a mouse model lacking the V1b receptor gene (V1bR-/-). Under resting conditions, circulating concentrations of ACTH and corticosterone were lower in V1bR-/- mice compared with WT mice (V1bR+/+). The normal increase in circulating ACTH levels in response to exogenous administration of AVP was impaired in V1bR-/- mice, while corticotropin-releasing hormone-stimulated ACTH release in the V1bR-/- mice was not significantly different from that in the V1bR+/+ mice. AVP-induced ACTH release from primary cultured pituitary cells in V1bR-/- mice was also blunted. Furthermore, the increase in ACTH after a forced swim stress was significantly suppressed in V1bR-/- mice. Our results clearly demonstrate that the V1b receptor plays a crucial role in regulating hypothalamic-pituitary-adrenal axis activity. It does this by maintaining ACTH and corticosterone levels, not only under stress but also under basal conditions.
    Tipo de documento:
    Referencia
    Referencia del producto:
    Múltiplo
    Nombre del producto:
    Múltiplo
  • A new function for the fragile X mental retardation protein in regulation of PSD-95 mRNA stability. 17417632

    Fragile X syndrome (FXS) results from the loss of the fragile X mental retardation protein (FMRP), an RNA-binding protein that regulates a variety of cytoplasmic mRNAs. FMRP regulates mRNA translation and may be important in mRNA localization to dendrites. We report a third cytoplasmic regulatory function for FMRP: control of mRNA stability. In mice, we found that FMRP binds, in vivo, the mRNA encoding PSD-95, a key molecule that regulates neuronal synaptic signaling and learning. This interaction occurs through the 3' untranslated region of the PSD-95 (also known as Dlg4) mRNA, increasing message stability. Moreover, stabilization is further increased by mGluR activation. Although we also found that the PSD-95 mRNA is synaptically localized in vivo, localization occurs independently of FMRP. Through our functional analysis of this FMRP target we provide evidence that dysregulation of mRNA stability may contribute to the cognitive impairments in individuals with FXS.
    Tipo de documento:
    Referencia
    Referencia del producto:
    MAB2160
    Nombre del producto:
    Anti-Fragile X Mental Retardation Protein Antibody, clone 1C3
  • Comparative expression analysis of the MAGED genes during embryogenesis and brain development. 15162511

    The MAGED gene subfamily contains three genes in mouse and four in human. The MAGED1, D2, and D3 proteins are highly conserved between mouse and human, whereas paralogues are less conserved between each other. This finding suggests that each MAGED protein exerts a distinct function. To get a better insight into their physiological roles, we have analyzed their expression patterns during embryogenesis and brain development. In the mouse, Maged3 expression is restricted to the central nervous system where it was mostly detected in postmitotic neurons. Maged2 is mainly expressed in tissues of mesodermal origin. The expression pattern of Maged1 roughly summarizes that of Maged2 and Maged3; however, contrary to that of Maged3, it includes the proliferative zones of the nervous system. We observed a discrepancy between Maged1 expression levels of RNA and protein, suggesting that its expression is regulated at a posttranscriptional level during the mouse development.
    Tipo de documento:
    Referencia
    Referencia del producto:
    03-248
    Nombre del producto:
    RIPAb+™ pan Ago - RIP Validated Antibody and Primer Set
  • Familiar taste induces higher dendritic levels of activity-regulated cytoskeleton-associated protein in the insular cortex than a novel one. 21921210

    The immediate early gene (IEG) Arc is known to play an important role in synaptic plasticity; its protein is locally translated in the dendrites where it has been involved in several types of plasticity mechanisms. Because of its tight coupling with neuronal activity, Arc has been widely used as a tool to tag behaviorally activated networks. However, studies examining the modulation of Arc expression during and after learning have yielded somewhat contradictory results. Although some have reported that higher levels of Arc were induced by initial acquisition of a task rather than by reinstating a learned behavior, others have failed to observe such habituation of Arc transcription. Moreover, most of these studies have focused on the mRNA and, surprisingly, relatively little is known about how learning can affect Arc protein expression levels. Here we used taste recognition memory and examined Arc protein expression in the insular cortex of rats at distinct times during taste memory formation. Interestingly, we found that more Arc protein was induced by a familiar rather than by a novel taste. Moreover, this increase was inhibited by post-trial intrahippocampal anisomycin injections, a treatment known to inhibit safe-taste memory consolidation. In addition, confocal microscopy analysis of immunofluorescence stained tissue revealed that the proportion of IC neurons expressing Arc was the same in animals exposed to novel and familiar taste, but Arc immunoreactivity in dendrites was dramatically higher in rats exposed to the familiar taste. These results provide novel insights on how experience affects cortical plasticity.
    Tipo de documento:
    Referencia
    Referencia del producto:
    Múltiplo
    Nombre del producto:
    Múltiplo
  • Tissue engineering the monosynaptic circuit of the stretch reflex arc with co-culture of embryonic motoneurons and proprioceptive sensory neurons. 22594977

    The sensory circuit of the stretch reflex arc is composed of intrafusal muscle fibers and their innervating proprioceptive neurons that convert mechanical information regarding muscle length and tension into action potentials that synapse onto the homonymous motoneurons in the ventral spinal cord which innervate the extrafusal fibers of the same muscle. To date, the in vitro synaptic connection between proprioceptive sensory neurons and spinal motoneurons has not been demonstrated. A functional in vitro system demonstrating this connection would enable the understanding of feedback by the integration of sensory input into the spinal reflex arc. Here we report a co-culture of rat embryonic motoneurons and proprioceptive sensory neurons from dorsal root ganglia (DRG) in a defined serum-free medium on a synthetic silane substrate (DETA). Furthermore, we have demonstrated functional synapse formation in the co-culture by immunocytochemistry and electrophysiological analysis. This work will be valuable for enabling in vitro model systems for the study of spinal motor control and related pathologies such as spinal cord injury, muscular dystrophy and spasticity by improving our understanding of the integration of the mechanosensitive feedback mechanism.
    Tipo de documento:
    Referencia
    Referencia del producto:
    MAB365
    Nombre del producto:
    Anti-Nerve Growth Factor Receptor Antibody, extracellular, clone 192-IgG
  • Orchestrated experience-driven Arc responses are disrupted in a mouse model of Alzheimer's disease. 22922786

    Experience-induced expression of immediate-early gene Arc (also known as Arg3.1) is known to be important for consolidation of memory. Using in vivo longitudinal multiphoton imaging, we found orchestrated activity-dependent expression of Arc in the mouse extrastriate visual cortex in response to a structured visual stimulation. In wild-type mice, the amplitude of the Arc response in individual neurons strongly predicted the probability of reactivation by a subsequent presentation of the same stimulus. In a mouse model of Alzheimer's disease, this association was markedly disrupted in the cortex, specifically near senile plaques. Neurons in the vicinity of plaques were less likely to respond, but, paradoxically, there were stronger responses in those few neurons around plaques that did respond. To the extent that the orchestrated pattern of Arc expression reflects nervous system responses to and physiological consolidation of behavioral experience, the disruption in Arc patterns reveals plaque-associated interference with neural network integration.
    Tipo de documento:
    Referencia
    Referencia del producto:
    MAB377
    Nombre del producto:
    Anti-NeuN Antibody, clone A60
  • Essential roles for the Abl and Arg tyrosine kinases in neurulation. 9883720

    The Abl and Arg tyrosine kinases play fundamental roles in the development and function of the central nervous system. Arg is most abundant in adult mouse brain, especially in synapse-rich regions. arg(-/-) mice develop normally but exhibit multiple behavioral abnormalities, suggesting that arg(-/-) brains suffer from defects in neuronal function. Embryos deficient in both Abl and Arg suffer from defects in neurulation and die before 11 days postcoitum (dpc). Although they divide normally, abl(-/-)arg(-/-) neuroepithelial cells display gross alterations in their actin cytoskeleton. We find that Abl and Arg colocalize with each other and with actin microfilaments at the apical surface of the developing neuroepithelium. Thus, Abl and Arg play essential roles in neurulation and can regulate the structure of the actin cytoskeleton.
    Tipo de documento:
    Referencia
    Referencia del producto:
    14-460
    Nombre del producto:
    Arg Protein, active, 10 µg
  • Nuclear receptor LRH-1 induces the reproductive neuropeptide kisspeptin in the hypothalamus. 23504956

    The differential expression and secretion of the neuropeptide kisspeptin from neurons in the arcuate (Arc) and anteroventral periventricular (AVPV) nuclei of the hypothalamus coordinate the temporal release of pituitary gonadotropins that control the female reproductive cycle. However, the molecular basis for this differential regulation is incompletely understood. Here, we report that liver receptor homolog-1 (LRH-1), a member of the nuclear receptor superfamily, is expressed in kisspeptin neurons in the Arc but not in the AVPV in female mice. LRH-1 binds directly to the kisspeptin (Kiss1) promoter and stimulates Kiss1 transcription. Deletion of LRH-1 from kisspeptin neurons in mice decreased Kiss1 expression in the Arc, leading to reduced plasma FSH levels, dysregulated follicle maturation, and prolongation of the estrous cycle. Conversely, overexpression of LRH-1 in kisspeptin neurons increased Arc Kiss1 expression and plasma FSH concentrations. These studies provide a molecular basis for the differential regulation of basal kisspeptin expression in Arc and AVPV neurons and reveal a prominent role for LRH-1 in hypothalamus in regulating the female reproductive axis.
    Tipo de documento:
    Referencia
    Referencia del producto:
    17-20000
    Nombre del producto:
    Magna ChIP™ G Tissue Kit