Oxytocin Receptor Binding Sites in the Periphery of the Neonatal Prairie Vole

The oxytocin receptor (OXTR) has been observed in the periphery of neonatal C57BL/6J mice (Mus musculus), including facial regions and the anogenital area. In those studies, ligand specificity was confirmed with a congenital OXTR knockout mouse as well as competitive binding techniques. The aim of this study was to determine if OXTR is present in the same peripheral sites in the neonatal prairie vole (Microtus ochrogaster) for cross-species comparisons. Receptor autoradiography was performed on 20 μm sagittal sections of whole postnatal day 0 (P0) male and female prairie voles using the 125iodinated-ornithine vasotocin ([125I]-OVTA) radioligand. A competition binding assay was used to assess the selectivity of [125I]-OVTA for peripheral OXTR. Radioactive ligand (0.05 nM [125I]-OVTA) was competed against concentrations of 0 and 1000 nM excess unlabeled oxytocin (OXT). Previously identified regions of significant OXTR ligand binding in the mouse were analyzed for comparison: rostral and lateral periodontium, olfactory epithelium, ciliary bodies of the eye, whisker pads, adrenal gland, and anogenital area. We also evaluated the liver and scapular brown adipose tissue, which displayed strong but non-specific signal on film in mice. While there were some areas that showed conserved OXTR ligand binding in the prairie vole (e.g., ciliary body of the eye and the anogenital area), areas showing OXTR ligand binding in the neonatal prairie vole were not identical to OXTR ligand binding in the periphery of the C57BL/6J neonatal mouse. Further, some of the regions measured in the prairie vole suggest sex differences in OXTR ligand binding. Collectively, as is well-established in the central nervous system, these data indicate that patterns of OXTR ligand binding in the infant periphery are species-specific

Evolution of a behavior-linked microsatellite-containing element in the 5' flanking region of the primate AVPR1A gene

<p>Abstract</p> <p>Background</p> <p>The arginine vasopressin V1a receptor (V1aR) modulates social cognition and behavior in a wide variety of species. Variation in a repetitive microsatellite element in the 5' flanking region of the V1aR gene (<it>AVPR1A</it>) in rodents has been associated with variation in brain V1aR expression and in social behavior. In humans, the 5' flanking region of <it>AVPR1A </it>contains a tandem duplication of two ~350 bp, microsatellite-containing elements located approximately 3.5 kb upstream of the transcription start site. The first block, referred to as DupA, contains a polymorphic (GT)₂₅microsatellite; the second block, DupB, has a complex (CT)₄-(TT)-(CT)₈-(GT)₂₄polymorphic motif, known as RS3. Polymorphisms in RS3 have been associated with variation in sociobehavioral traits in humans, including autism spectrum disorders. Thus, evolution of these regions may have contributed to variation in social behavior in primates. We examined the structure of these regions in six ape, six monkey, and one prosimian species.</p> <p>Results</p> <p>Both tandem repeat blocks are present upstream of the <it>AVPR1A </it>coding region in five of the ape species we investigated, while monkeys have only one copy of this region. As in humans, the microsatellites within DupA and DupB are polymorphic in many primate species. Furthermore, both single (lacking DupB) and duplicated alleles (containing both DupA and DupB) are present in chimpanzee (<it>Pan troglodytes</it>) populations with allele frequencies of 0.795 and 0.205 for the single and duplicated alleles, respectively, based on the analysis of 47 wild-caught individuals. Finally, a phylogenetic reconstruction suggests two alternate evolutionary histories for this locus.</p> <p>Conclusion</p> <p>There is no obvious relationship between the presence of the RS3 duplication and social organization in primates. However, polymorphisms identified in some species may be useful in future genetic association studies. In particular, the presence of both single and duplicated alleles in chimpanzees provides a unique opportunity to assess the functional role of this duplication in contributing to variation in social behavior in primates. While our initial studies show no signs of directional selection on this locus in chimps, pharmacological and genetic association studies support a potential role for this region in influencing V1aR expression and social behavior.</p

Entrevista a Elina Scheja

Versión en inglés disponible en la Biblioteca Digital del IDR

Special : multidimensional measures during the covid-19 pandemic

These articles are drawn from a high-level online Side Event at the 75th UN General Assembly September (2020) entitled 'Poverty at a Crossroads: Using Leadership and the Multidimensional Poverty Indices to Build Back Better.' Some dimensions of poverty measured by MPI are: resources; choice; power and voice; and human security. This framework embraces complexity, allowing theories of change to be developed in order to break siloed divisions and poverty traps. As the pandemic continues to rage through many parts of the planet, the session evoked powerful messages of reflection, leadership, collaboration and hope

Role of Soluble Epoxide Hydrolase in Postischemic Recovery of Heart Contractile Function

Cytochrome P450 epoxygenases metabolize arachidonic acid to epoxyeicosatrienoic acids (EETs) which are converted to dihydroxyeicosatrienoic acids (DHETs) by soluble epoxide hydrolase (Ephx2, sEH). To examine the functional role of sEH in the heart, mice with targeted disruption of the Ephx2 gene were studied. Hearts from sEH null mice have undetectable levels of sEH mRNA and protein and cannot convert EETs to DHETs. sEH null mice have normal heart anatomy and basal contractile function, but have higher fatty acid epoxide:diol ratios in plasma and cardiomyocyte cell culture media compared with wild type (WT). sEH null hearts have improved recovery of left ventricular developed pressure (LVDP) and less infarction compared with WT hearts after 20 minutes ischemia. Perfusion with the putative EET receptor antagonist 14,15-epoxyeicosa-5(Z)-enoic acid (10 to 100 nmol/L) before ischemia abolishes this cardioprotective phenotype. Inhibitor studies demonstrate that perfusion with phosphatidylinositol-3 kinase (PI3K) inhibitors wortmannin (200 nmol/L) or LY294002 (5 μmol/L), the ATP-sensitive K+ channel (KATP) inhibitor glibenclamide (1 μmol/L), the mitochondrial KATP (mitoKATP) inhibitor 5-hydroxydecanoate (100 to 200 μmol/L), or the Ca2+-sensitive K+ channel (KCa) inhibitor paxilline (10 μmol/L) abolishes the cardioprotection in sEH null hearts. Consistent with increased activation of the PI3K cascade, sEH null mice exhibit increased cardiac expression of glycogen synthase kinase-3β (GSK-3β) phospho-protein after ischemia. Together, these data suggest that targeted disruption of sEH increases the availability of cardioprotective EETs that work by activating PI3K signaling pathways and K+ channels

Colocalization of Oxtr with Prader-Willi Syndrome transcripts in the trigeminal ganglion of neonatal mice

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