Selective breeding for high anxiety introduces a synonymous SNP that increases neuropeptide S receptor activity

The Journal of Neuroscience : the Official Journal of the Society for Neuroscience
David A SlatteryInga D Neumann

Abstract

Neuropeptide S (NPS) has generated substantial interest due to its anxiolytic and fear-attenuating effects in rodents, while a corresponding receptor polymorphism associated with increased NPS receptor (NPSR1) surface expression and efficacy has been implicated in an increased risk of panic disorder in humans. To gain insight into this paradox, we examined the NPS system in rats and mice bred for high anxiety-related behavior (HAB) versus low anxiety-related behavior, and, thereafter, determined the effect of central NPS administration on anxiety- and fear-related behavior. The HAB phenotype was accompanied by lower basal NPS receptor (Npsr1) expression, which we could confirm via in vitro dual luciferase promoter assays. Assessment of shorter Npsr1 promoter constructs containing a sequence mutation that introduces a glucocorticoid receptor transcription factor binding site, confirmed via oligonucleotide pull-down assays, revealed increased HAB promoter activity-an effect that was prevented by dexamethasone. Analogous to the human NPSR1 risk isoform, functional analysis of a synonymous single nucleotide polymorphism in the coding region of HAB rodents revealed that it caused a higher cAMP response to NPS stimulation. Assessment...Continue Reading

Citations

Jul 26, 2015·Biological Psychiatry·Inga D Neumann, David A Slattery
Oct 16, 2015·Acta Neuropsychiatrica·Artur PalaszRyszard Wiaderkiewicz
Oct 16, 2015·Brain Structure & Function·Csaba AdoriTomas Hökfelt
May 27, 2017·The European Journal of Neuroscience·Xiaobin LiuRainer K Reinscheid
Aug 15, 2017·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·Thomas Grund, Inga D Neumann
Jun 14, 2018·Physiological Reviews·Benjamin Jurek, Inga D Neumann
Sep 18, 2018·Genes, Brain, and Behavior·Doris S Bayerl, Oliver J Bosch
Sep 15, 2019·Translational Psychiatry·Anna K SchmidtnerInga D Neumann
Jun 10, 2020·Molecular Psychiatry·Valery Grinevich, Inga D Neumann
Aug 17, 2018·Cell and Tissue Research·Thomas Grund, Inga D Neumann
May 15, 2020·Molecular Psychiatry·Shannon J MooreVictor A Cazares
Mar 20, 2020·Neuropharmacology·Volker NeugebauerFrank Porreca
May 1, 2021·Pharmaceuticals·Rainer K Reinscheid, Chiara Ruzza
Aug 9, 2020·Current Biology : CB·Carlos PantojaHerwig Baier

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