Abstract:
Neuropeptides are mostly expressed in regions of the brain responsible for learning and memory and are centrally involved in cognitive pathways. The majority of neuropeptide research has been performed in animal models; with acknowledged differences between species, more research into the role of neuropeptides in humans is necessary to understand their contribution to higher cognitive function. In this study, we investigated the influence of genetic polymorphisms in neuropeptide genes on verbal learning and memory. Variants in genes encoding neuropeptides and neuropeptide receptors were tested for association with learning and memory measures using the Hopkins Verbal Learning Test-Revised (HVLT-R) in a healthy cohort of individuals (n = 597). The HVLT-R is a widely used task for verbal learning and memory assessment and provides five sub-scores: recall, delay, learning, retention, and discrimination. To determine the effect of candidate variants on learning and memory performance, genetic association analyses were performed for each HVLT-R sub-score with over 1300 genetic variants from 124 neuropeptide and neuropeptide receptor genes, genotyped on Illumina OmniExpress BeadChip arrays. This targeted analysis revealed numerous suggestive associations between HVLT-R test scores and neuropeptide and neuropeptide receptor gene variants; candidates include the SCG5, IGFR1, GALR1, OXTR, CCK, and VIPR1 genes. Further characterization of these genes and their variants will improve our understanding of the genetic contribution to learning and memory and provide insight into the importance of the neuropeptide network in humans.
摘要:
神经肽主要在负责学习和记忆的大脑区域中表达,并且主要参与认知途径。大多数神经肽研究已经在动物模型中进行;与公认的物种之间的差异,有必要对神经肽在人类中的作用进行更多的研究,以了解它们对更高的认知功能的贡献。在这项研究中,我们研究了神经肽基因的遗传多态性对言语学习和记忆的影响。在健康的个体队列(n=597)中,使用Hopkins言语学习测试-修订版(HVLT-R)测试编码神经肽和神经肽受体的基因中的变体与学习和记忆测量的关联。HVLT-R是一项广泛用于口头学习和记忆评估的任务,并提供五个子分数:回忆,延迟,学习,保留,和歧视。为了确定候选变体对学习和记忆表现的影响,对来自124个神经肽和神经肽受体基因的1300多个遗传变异的每个HVLT-R子评分进行遗传关联分析,在IlluminaOmniExpressBeadChip阵列上进行基因分型。这种有针对性的分析揭示了HVLT-R测试分数与神经肽和神经肽受体基因变体之间的许多暗示性关联;候选包括SCG5,IGFR1,GALR1,OXTR,CCK,和VIPR1基因。对这些基因及其变体的进一步表征将提高我们对遗传对学习和记忆的贡献的理解,并提供对神经肽网络在人类中的重要性的见解。