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 organization: | Molecular and Integrative Biosciences Research Programme SLEEPWELL Research Program Medicum Institute for Molecular Medicine Finland Department of Psychology and Logopedics Neuroscience Center STEMM - Stem Cells and Metabolism Research Program Helsinki In Vivo Animal Imaging Platform (HAIP) Department of Pharmacology Iiris Hovatta / Principal Investigator Genetics Mind and Matter |
Date: | 2019-12-19 |
Language: | eng |
Number of pages: | 13 |
Belongs to series: | Scientific Reports |
ISSN: | 2045-2322 |
DOI: | https://doi.org/10.1038/s41598-019-55947-5 |
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 |
Peer reviewed: | Yes |
Rights: | cc_by |
Usage restriction: | openAccess |
Self-archived version: | publishedVersion |
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