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首页> 外文期刊>The European Journal of Neuroscience >FKBP5 polymorphisms influence pre‐learning stress‐induced alterations of learning and memory
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FKBP5 polymorphisms influence pre‐learning stress‐induced alterations of learning and memory

机译：FKBP5多态性影响预学习压力引起的学习和记忆的改变

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摘要

FK506 binding protein 51 (FKBP5) is a co‐chaperone of heat shock protein 90 and significantly influences glucocorticoid receptor sensitivity. Single nucleotide polymorphisms (SNPs) in the FKBP5 gene are associated with altered hypothalamus–pituitary–adrenal (HPA) axis function, changes in the structure and function of several cognitive brain areas, and increased susceptibility to post‐traumatic stress disorder, major depression, bipolar disorder and suicidal events. The mechanisms underlying these associations are largely unknown, but it has been speculated that the influence of these SNPs on emotional memory systems may play a role. In the present study, 112 participants were exposed to the socially evaluated cold pressor test (stress) or control (no stress) conditions immediately prior to learning a list of 42 words. Participant memory was assessed immediately after learning (free recall) and 24 h later (free recall and recognition). Participants provided a saliva sample that enabled the genotyping of three FKBP5 polymorphisms: rs1360780, rs3800373 and rs9296158. Results showed that stress impaired immediate recall in risk allele carriers. More importantly, stress enhanced long‐term recall and recognition memory in non‐carriers of the risk alleles, effects that were completely absent in risk allele carriers. Follow‐up analyses revealed that memory performance was correlated with salivary cortisol levels in non‐carriers, but not in carriers. These findings suggest that FKBP5 risk allele carriers may possess a sensitized stress response system, perhaps specifically for stress‐induced changes in corticosteroid levels, which might aid our understanding of how SNPs in the FKBP5 gene confer increased risk for stress‐related psychological disorders and their related phenotypes.
机译：FK506结合蛋白51（FKBP5）是热休克蛋白90的共伴侣，显着影响糖皮质激素受体敏感性。 FKBP5基因中的单核苷酸多态性（SNP）与次耳垂体 - 肾上腺（HPA）轴功能改变有关，几种认知脑区域的结构和功能的变化，以及对创伤后应激障碍，主要抑郁症的易感性增加，双相障碍和自杀事件。这些关联的基本机制很大程度上是未知的，但已经推测，这些SNP对情绪记忆系统的影响可能起到作用。在本研究中，在学习42个单词的列表之前，将112名参与者暴露于社会评估的冷压力测试（应力）或控制（没有应力）条件。学习（免费召回）和24小时后立即评估参与者内存（免费召回和识别）。参与者提供了一种唾液样本，使三种FKBP5多态性进行基因分型：RS1360780，RS3800373和RS9296158。结果表明，风险等位基因载体立即召回压力受损。更重要的是，应力增强了风险等位基因的非载体中的长期召回和识别记忆，风险等位基因载体中完全不存在的效果。随访分析显示，内存性能与非载波中的唾液皮质醇水平相关，但不在载体中相关。这些发现表明FKBP5风险等位基因载体可能具有敏化的应力响应系统，也许特别是对于皮质类固醇水平的压力诱导的变化，这可能有助于我们理解FKBP5基因中的SNP如何增加压力相关的心理障碍风险和其相关表型。

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