Alacreu-Crespo Adrián, Olié Emilie, Manière Maxime, Deverdun Jeremy, Lebars Emmanuelle, Corbani Maithé, Guillon Gilles, Courtet Philippe
FondaMental Foundation, Créteil, France.
Department of Psychology and Sociology, Area of personality, Assessment and Psychological Treatment, University of Zaragoza, C/ Atarazana 4, Teruel, Aragón, 44003, Spain.
BMC Neurosci. 2025 Jul 17;26(1):42. doi: 10.1186/s12868-025-00963-7.
In humans, vasopressin AVP1BR receptor (hV) plays key roles in hypothalamic-pituitary-adrenal (HPA) axis regulation and social behavior. Three hV 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 hV 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 hV variants: K65/G191/R364 (wild type), G191R, K65N and/or R364H. Brain functional activity was investigated in 35 healthy men with different hV variants during an fMRI implicit emotional recognition paradigm. IPs accumulation after arginine vasopressin stimulation was much reduced in cells expressing hV 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 hV polymorphisms could be candidates as biomarkers of psychiatric disorders. Moreover, hV may be a pharmacological target if these polymorphisms are considered.
在人类中，血管加压素AVP1BR受体（hV）在下丘脑-垂体-肾上腺（HPA）轴调节和社会行为中发挥关键作用。三种hV多态性，即rs35369693（K65N）、rs28632197（R364H）和rs33990840（G191R），与HPA轴功能和社会行为改变的精神障碍有关。本研究的目的是探讨hV的药理学特性，该特性是转染细胞中多态性的函数，以及在具有不同AVP1BR多态性的志愿者的情感任务中的大脑功能。在表达不同hV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35名具有不同hV变体的健康男性中，在功能磁共振成像（fMRI）隐性情绪识别范式期间研究大脑功能活动。精氨酸加压素刺激后，表达hV K65N和/或R364H的细胞中IPs积累显著减少，而表达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。在愤怒与中性面孔视觉任务期间，K65/R364单倍型纯合子中运动区、视觉区、额下回区域、海马体和壳核的激活高于杂合子。由于G191多态性频率较低，分析未纳入具有该多态性的参与者。不同的hV多态性可能是精神障碍生物标志物的候选者。此外，如果考虑这些多态性，hV可能是一个药理学靶点。
