FKBP5 polymorphisms influence pre-learning stress-induced alterations of learning and memory.
FKBP5 polymorphisms influence pre-learning stress-induced alterations of learning and memory.
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FKBP5 多态性影响学习前压力引起的学习和记忆改变。
DOI：
10.1111/ejn.13514
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发表时间：
2017
期刊：
影响因子：
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通讯作者：
Rorabaugh,BoydR
中科院分区：
文献类型：
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作者：
Zoladz,PhillipR;Dailey,AlisonM;Nagle,HannahE;Fiely,MirandaK;Mosley,BrianneE;Brown,CallieM;Duffy,TessaJ;Scharf,AmandaR;Earley,McKennaB;Rorabaugh,BoydR
FK 506结合蛋白51（FKBP 5）是热休克蛋白90的共伴侣，显著影响糖皮质激素受体敏感性。FKBP 5基因的单核苷酸多态性（SNPs）与下丘脑-垂体-肾上腺（HPA）轴功能改变、几个认知脑区的结构和功能改变以及创伤后应激障碍、重性抑郁症、双相情感障碍和自杀事件易感性增加相关。这些关联背后的机制在很大程度上是未知的，但据推测，这些SNPs对情绪记忆系统的影响可能发挥了作用。在本研究中，112名参与者在学习42个单词的列表之前立即暴露于社会评估的冷加压测试（压力）或对照（无压力）条件。参与者的记忆力在学习后立即（自由回忆）和24小时后（自由回忆和识别）进行评估。参与者提供了一份唾液样本，该样本能够对三种FKBP 5多态性进行基因分型：rs 1360780、rs3800373和rs 9296158。结果表明，压力损害了风险等位基因携带者的即时回忆。更重要的是，压力增强了非风险等位基因携带者的长期回忆和识别记忆，这在风险等位基因携带者中完全不存在。随访分析显示，记忆力表现与非携带者的唾液皮质醇水平相关，但与携带者无关。这些发现表明，FKBP 5风险等位基因携带者可能拥有一个敏感的应激反应系统，可能专门针对应激诱导的皮质类固醇水平变化，这可能有助于我们理解FKBP 5基因中的SNP如何增加应激相关心理障碍及其相关表型的风险。
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 theFKBP5gene 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 threeFKBP5polymorphisms: 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 thatFKBP5risk 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 theFKBP5gene confer increased risk for stress‐related psychological disorders and their related phenotypes.