WWC1 genotype modulates age-related decline in episodic memory function across the adult life span.
WWC1 genotype modulates age-related decline in episodic memory function across the adult life span.
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DOI：
10.1016/j.biopsych.2013.09.036
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发表时间：
2014-05-01
影响因子：
10.6
通讯作者：
Mattay VS
中科院分区：
文献类型：
--
作者：
Muse J;Emery M;Sambataro F;Lemaitre H;Tan HY;Chen Q;Kolachana BS;Das S;Callicott JH;Weinberger DR;Mattay VS
众所周知，情景记忆（EM）会随着年龄的增长而下降，而且下降的速度因人而异。WWC1基因中的单核苷酸多态性（rs17070145）编码对长期增强（LTP）和记忆巩固至关重要的KIBRA蛋白，此前已通过fMRI与EM表现以及EM任务期间海马参与的差异相关。在目前的研究中，我们利用功能磁共振成像（fMRI）探讨了这种多态性对成人一生中EM相关活动和认知表现的影响。232名健康的白人受试者（年龄在18-89岁之间）在fMRI扫描期间完成了一系列认知测试和EM任务。WWC1 T携带者的延迟回忆表现显著优于CC个体（p=0.006）。在WWC1基因型组之间，年龄增长与即时和延迟回忆得分之间的关系也有显著差异（p=0.01）。除了编码和检索过程中海马形成（HF）激活的年龄相关下降（p<0.05; FDRSVC-HF-ROI）外，我们还通过WWC1基因型相互作用观察到编码和检索过程中海马形成（HF）激活的年龄。CC组HF活性与年龄增长呈显著负相关，而T携带者组无显著负相关（左HF p=0.04，编码检索时R-Z相关差异；右HF p=0.0008，检索时R-Z相关差异）。我们的研究结果提供了rs17070145多态性与海马区神经元活性增加之间的动态关系的证据。
Episodic memory (EM) is known to decline with age and the rate of decline is variable across individuals. A single nucleotide polymorphism (rs17070145) in the WWC1 gene that encodes the KIBRA protein critical for long term potentiation (LTP) and memory consolidation has previously been associated with EM performance as well as differences in hippocampal engagement during EM tasks using fMRI. In the current study, we explore the effect of this polymorphism on EM related activity and cognitive performance across the adult lifespan using fMRI. Two hundred thirty-two healthy, Caucasian subjects (age range 18–89 years) completed a battery of cognitive tests as well as an EM task during an fMRI scan. WWC1 T carriers had significantly better delayed recall performance than CC individuals (p=0.006). The relationship between increasing age and recall scores, both immediate and delayed, was also significantly different between WWC1 genotype groups (p=0.01). In addition to the age-related decline in hippocampal formation (HF) activation bilaterally during encoding and retrieval (p<0.05; FDRSVC-HF-ROI), we observed an age by WWC1 genotype interaction on activation in the HF during encoding and retrieval. The CC group showed a significant negative association between HF activity and increasing age while no such association was observed in the T carrier group (left HF p=0.04; R-Z correlation difference during encoding and retrieval; right HF p=0.0008; R-Z correlation difference during retrieval). Our results provide evidence of a dynamic relationship between rs17070145 polymorphism and increasing age on neuronal activity in the hippocampal region.
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