The bradykinin system in stress and anxiety in humans and mice

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Rouhiainen , A , Kulesskaya , N , Mennesson , M , Misiewicz , Z , Sipila , T , Sokolowska , E , Trontti , K , Urpa , L , McEntegart , W , Saarnio , S , Hyytia , P & Hovatta , I 2019 , ' The bradykinin system in stress and anxiety in humans and mice ' , Scientific Reports , vol. 9 , 19437 . https://doi.org/10.1038/s41598-019-55947-5

Title: The bradykinin system in stress and anxiety in humans and mice
Author: Rouhiainen, Ari; Kulesskaya, Natalia; Mennesson, Marie; Misiewicz, Zuzanna; Sipila, Tessa; Sokolowska, Ewa; Trontti, Kalevi; Urpa, Lea; McEntegart, William; Saarnio, Suvi; Hyytia, Petri; Hovatta, Iiris
Contributor: University of Helsinki, Molecular and Integrative Biosciences Research Programme
University of Helsinki, Molecular and Integrative Biosciences Research Programme
University of Helsinki, Molecular and Integrative Biosciences Research Programme
University of Helsinki, Institute for Molecular Medicine Finland
University of Helsinki, Molecular and Integrative Biosciences Research Programme
University of Helsinki, Molecular and Integrative Biosciences Research Programme
University of Helsinki, SLEEPWELL Research Program
University of Helsinki, Molecular and Integrative Biosciences Research Programme
University of Helsinki, STEMM - Stem Cells and Metabolism Research Program
University of Helsinki, Helsinki In Vivo Animal Imaging Platform (HAIP)
University of Helsinki, Department of Psychology and Logopedics
Date: 2019-12-19
Language: eng
Number of pages: 13
Belongs to series: Scientific Reports
ISSN: 2045-2322
URI: http://hdl.handle.net/10138/312445
Abstract: Pharmacological research in mice and human genetic analyses suggest that the kallikrein-kinin system (KKS) may regulate anxiety. We examined the role of the KKS in anxiety and stress in both species. In human genetic association analysis, variants in genes for the bradykinin precursor (KNG1) and the bradykinin receptors (BDKRB1 and BDKRB2) were associated with anxiety disorders (p <0.05). In mice, however, neither acute nor chronic stress affected B1 receptor gene or protein expression, and B1 receptor antagonists had no effect on anxiety tests measuring approach-avoidance conflict. We thus focused on the B2 receptor and found that mice injected with the B2 antagonist WIN 64338 had lowered levels of a physiological anxiety measure, the stress-induced hyperthermia (SIH), vs controls. In the brown adipose tissue, a major thermoregulator, WIN 64338 increased expression of the mitochondrial regulator Pgc1 alpha and the bradykinin precursor gene Kng2 was upregulated after cold stress. Our data suggests that the bradykinin system modulates a variety of stress responses through B2 receptor-mediated effects, but systemic antagonists of the B2 receptor were not anxiolytic in mice. Genetic variants in the bradykinin receptor genes may predispose to anxiety disorders in humans by affecting their function.
Subject: DORSAL PERIAQUEDUCTAL GRAY
KALLIKREIN-KININ SYSTEM
B-2 RECEPTOR
ASSOCIATION ANALYSIS
GENE-EXPRESSION
ADMINISTERED BRADYKININ
RAT
ANTAGONIST
DISORDER
BRAIN
3112 Neurosciences
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