A pharmacological and brain imaging study of human vasopressin AVP1BR receptor functional polymorphisms.

IF 2.3 4区 医学 Q3 NEUROSCIENCES
Adrián Alacreu-Crespo, Emilie Olié, Maxime Manière, Jeremy Deverdun, Emmanuelle Lebars, Maithé Corbani, Gilles Guillon, Philippe Courtet
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引用次数: 0

Abstract

In humans, vasopressin AVP1BR receptor (hV1B) plays key roles in hypothalamic-pituitary-adrenal (HPA) axis regulation and social behavior. Three hV1B polymorphisms, rs35369693 (K65N), rs28632197 (R364H) and rs33990840 (G191R), have been related to psychiatric disorders with altered HPA axis function and social behavior. The aim of this study was to explore hV1B pharmacological properties as a function of the polymorphism in transfected cells and the brain functioning in an emotional task in volunteers harboring different AVP1BR polymorphisms. Transfection rate, fluorescent imaging and inositol phosphate (IPs) accumulation were evaluated in HEK293 cells that expressed different hV1B variants: K65/G191/R364 (wild type), G191R, K65N and/or R364H. Brain functional activity was investigated in 35 healthy men with different hV1B variants during an fMRI implicit emotional recognition paradigm. IPs accumulation after arginine vasopressin stimulation was much reduced in cells expressing hV1B K65N and/or R364H, and increased in cells expressing G191R. Basal IPs accumulation, transfection rate, and fluorescent binding to plasma membrane were similar for all polymorphisms. During the anger vs. neutral face visualization task, activation of motor areas, visual areas, frontal sub-gyral area, hippocampus, and putamen was higher in homozygotes for the K65/R364 haplotype than in heterozygotes. Analyses did not include participants with the G191 polymorphism because of its low frequency. Different hV1B polymorphisms could be candidates as biomarkers of psychiatric disorders. Moreover, hV1B may be a pharmacological target if these polymorphisms are considered.

人抗利尿激素AVP1BR受体功能多态性的药理学和脑成像研究。
在人类中,抗利尿激素AVP1BR受体(hV1B)在下丘脑-垂体-肾上腺(HPA)轴调节和社会行为中起关键作用。三个hV1B多态性rs35369693 (K65N), rs28632197 (R364H)和rs33990840 (G191R)与HPA轴功能和社会行为改变的精神疾病有关。本研究的目的是探讨不同AVP1BR多态性的志愿者在转染细胞中hV1B的药理特性与多态性的关系,以及在情绪任务中的大脑功能。在表达不同hV1B变体:K65/G191/R364(野生型)、G191R、K65N和/或R364H的HEK293细胞中,评估转染率、荧光成像和肌醇磷酸(IPs)积累。在fMRI内隐情绪识别范式中,研究了35名不同hV1B变异的健康男性的脑功能活动。在表达hV1B K65N和/或R364H的细胞中,精氨酸加压素刺激后的IPs积累大大减少,而在表达G191R的细胞中,IPs积累增加。所有多态性的基础IPs积累、转染率和与质膜的荧光结合相似。在愤怒与中性面部视觉任务中,K65/R364单倍型纯合子的运动区、视觉区、额叶下回区、海马体和壳核的激活高于杂合子。分析没有包括G191多态性的参与者,因为其频率较低。不同的hV1B多态性可以作为精神疾病的生物标志物。此外,如果考虑到这些多态性,hV1B可能是一个药理靶点。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
BMC Neuroscience
BMC Neuroscience 医学-神经科学
CiteScore
3.90
自引率
0.00%
发文量
64
审稿时长
16 months
期刊介绍: BMC Neuroscience is an open access, peer-reviewed journal that considers articles on all aspects of neuroscience, welcoming studies that provide insight into the molecular, cellular, developmental, genetic and genomic, systems, network, cognitive and behavioral aspects of nervous system function in both health and disease. Both experimental and theoretical studies are within scope, as are studies that describe methodological approaches to monitoring or manipulating nervous system function.
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