APOE风险基因和性别差异对空间导航能力相关脑结构的影响

发布时间：2018-07-05 13:53

  本文选题：空间导航 + 性别　； 参考：《南京大学》2017年硕士论文

【摘要】：第一部分空间导航能力与海马亚区体积相关性的性别差异化研究目的:空间导航能力是一种非常重要的基本生活能力,包含了多个复杂的认知及感知过程,其能力受损与萎缩的海马体积明显相关。前人报道,性别不同所引起的空间导航行为学不同,但是这种差异的脑结构改变基础还不是很明确。本研究旨在研究正常年轻人中,性别对其空间导航能力的影响,以及其与海马体积、海马亚区体积的联系。材料与方法:通过志愿者招募流程,收入63名正常年轻志愿者纳入本研究(男33名,年龄24.00±1.27岁;女30名,年龄23.90±1.95岁)。所有被试者均进行了空间导航测试及头颅磁共振检查。空间导航测试使用PC版的隐藏任务测试(Hidden Goal Task,HGT),即视觉模拟的水迷宫(Morris Water Maze,MWM)测试进行,分别测试综合导航、环境导航、自我导航及延迟-环境导航能力;采用3D-T1加权成像序列进行颅脑高清结构像采集,并通过FreeSurfer软件分割及计算得到每个被试双侧海马亚区和海马整体的体积,FreeSurfer5.3.0将海马分为CA1、CA2_3、CA4_DG、下托(subiculum)、前下托(presubiculum)、海马裂(fissure)、海马伞(fimbria)以及无法分割的尾区(标记为hippocampus)8个亚区。全部受试者按照性别分为两组。利用两个独立样本T检验(two sample t test)对两组的各种空间导航能力、年龄、受教育程度做组间比较。用Pearson相关检验和偏相关检验对空间导航能力值与海马体积与海马亚区体积进行分析。结果:研究发现在正常年轻人中男性的综合空间导航能力较女性的差(男性:28.69±16.59;女性:22.33±6.27;p=0.047),两组的自我导航和环境导航比较没有统计学差异。在相关分析中发现,综合导航能力的差异与右侧海马前下托(r=0.313,p=0.013)和下托(r=0.262,p=0.040)的体积变化有关。结论:在健康年轻人中,男女的综合空间导航能力有差异,且这种差异与右侧海马前下托与下托的体积差异相关。这一研究强调了空间导航能力与海马亚区之间的关系,提示不同的海马亚区在空间导航中的不同作用,为下一步揭示空间导航差异的结构与功能基础打下了基础。第二部分APOE风险基因携带者中空间导航能力和脑白质纤维束特征的相关性研究目的:APOE ε4等位基因被认为是阿尔茨海默病(Alzheimer's disease,AD)的一个主要危险基因,空间导航能力受损及纤维束完整性受到破坏在老年人和AD患者中也非常常见。然而空间导航能力受损与纤维束完整性在APOE风险基因携带者中的相关性还不甚明确。本文旨在研究正常年轻人中APOE风险基因携带者中空间导航能力和纤维束特征的相关性。材料与方法:通过前章所述的志愿者招募流程及空间导航测试和头颅磁共振检查的60名被试抽取外周血进行基因型检测。用纤维束自动定量分析法(automating fiber-tract quantification,AFQ)分析脑内 20 条纤维束上各 100 个节点的各向异性分数(fractional anisotropy,FA)和平均扩散系数(mean diffusivity,MD)。全部受试者按照基因型分为三组。单因素方差分析和spearman相关检验分别用于对三组的空间导航能力、20条纤维束上的弥散张量指标做组间比较和相关性分析。结果:综合导航能力(p=0.627),自我导航能力(p=0.768)及环境导航能力(p=0.491)在三组APOE等位基因型(ε2/ε3、ε3/ε3、ε4/ε3)正常年轻人中均不存在组间显著差异。在20条纤维束的100个节点特征分析中发现,APOE ε3/ε3组较APOE ε2/ε3组的双侧丘脑辐射束(左侧:t=2.839,p=0.007;右侧:t=4.174,p=0.000)、胼胝体(膝部:t=2.487,p=0.016;压部:t=3.425,0.001)的 FA 值低,APOEε4/ε3 组较 APOEε2/ε3 组的胼胝体(压部:t=2.350,p=0.039)的 FA 值低。APOE ε4/ε3 组右侧弓形束(t=:-2.958,p=0.018)、左侧上纵束(t=-2.737,p=0.025)、肼胝体(压部:t=-3.208,p=0.008)MD 值较 APOEε2ε3 组高;APOEε3/ε3 组右侧扣带束(t=-3.211,p=0.002)MD 值较 APOE ε2/ε3 组高;而 APOE ε3/ε3 组较APOEε2/ε3组在左侧下额枕束额叶段(t=2.656,p=0.011)及右侧丘脑辐射束(t=2.738,p=0.009)MD值为低。在进一步的相关分析中发现:APOEε2/ε3组中右侧扣带束扣带回MD值与综合空间导航能力正相关(r=0.829,p=0.042)。结论:在正常年轻人中,APOE风险基因携带者与非携带者的空间导航能力未发现显著差异,但APOEε4携带者中纤维束完整性出现破坏。同时,APOEε2携带者中综合空间导航能力与纤维束完整性呈现正相关,提示APOE ε4基因可能是空间导航障碍的风险因素之一。
[Abstract]:The first part of the study on the correlation between the spatial navigation ability and the volume of the hippocampal subregion: the spatial navigation ability is a very important basic living ability, including a number of complex cognitive and perceptual processes, and its capacity is significantly related to the atrophy of the hippocampal volume. Behaviourology is different, but the basis of the changes in brain structure is not very clear. The purpose of this study is to study the effect of gender on its spatial navigation ability in normal young people, and its relationship with the volume of hippocampus and hippocampus. Materials and methods: 63 normal young volunteers were enrolled in the study through the volunteer recruitment process. Study (male 33, age 24 + 1.27 years; female 30, age 23.90 + 1.95 years old). All subjects carried out the space navigation test and head magnetic resonance examination. The space navigation test used the PC version of the Hidden Goal Task, HGT, that is, the visual analog water maze (Morris Water Maze, MWM) test, test the integrated navigation, ring respectively. Navigation, self navigation and delay - Environmental navigation ability; using the 3D-T1 weighted imaging sequence to collect high definition structure image of brain, and to divide and calculate the volume of the whole hippocampus and hippocampus of each trial by FreeSurfer software. FreeSurfer5.3.0 divides the hippocampus into CA1, CA2_3, CA4_DG, subiculum, and anterior lower (presubicu). Lum), fissure, fimbria, and undivided tail region (hippocampus) 8 sub regions. All subjects were divided into two groups according to sex. Using two independent samples, T test (two sample t test), the various spatial navigation ability, age, and education level of the two groups were compared. Pearson correlation test and partial phase were used. The value of spatial navigation ability and the volume of hippocampal volume and hippocampal subregion were analyzed by the test. Results: the results showed that the overall spatial navigation ability of male in normal young people was less than that of women (male: 28.69 + 16.59; female: 22.33 + 6.27; p=0.047). There was no statistical difference between the two groups of self navigation and environmental navigation. It is found that the difference in integrated navigation ability is related to the volume change of the right hippocampal anterior underlay (r=0.313, p=0.013) and the r=0.262 (p=0.040). Conclusion: in healthy young people, the comprehensive spatial navigation ability of men and women is different, and this difference is related to the volume difference between the anterior underlay and the underlay of the right hippocampus. This study emphasizes the spatial guidance. The relationship between the navigation ability and the subregion of the hippocampus suggests the different roles of different hippocampal subregions in spatial navigation, which lays the foundation for the next step to reveal the structural and functional basis of spatial navigation differences. The purpose of the study on the correlation of spatial navigation ability and white matter fiber characteristics in the second APOE risk gene carriers: APOE epsilon 4, etc. The allele is considered as a major risk gene for Alzheimer's disease (AD). Damage to space navigation and damage of fiber bundle integrity are also very common in elderly and AD patients. However, the correlation of spatial navigation impairment and fiber bundle integrity in APOE risk gene carriers is not clear. The purpose of this study is to study the correlation between spatial navigation and fiber bundle characteristics of APOE risk gene carriers in normal young people. Materials and methods: 60 subjects were tested for genotyping by the volunteers' recruitment process, space navigation test and head magnetic resonance examination in the previous chapter. Automating fiber-tract quantification (AFQ) analysis of the anisotropic fraction (fractional anisotropy, FA) and average diffusion coefficient (mean diffusivity, MD) of 100 nodes on 20 fibers in the brain (mean diffusivity, MD). All the subjects were divided into three groups according to the genotype. Single factor difference analysis and Spearman correlation test were used for the three groups. Inter group comparison and correlation analysis. Results: comprehensive navigation ability (p=0.627), self navigation ability (p=0.768) and environmental navigation ability (p=0.491) in three groups of APOE alleles (epsilon 3, epsilon 3, epsilon 4/ 3) were not significantly different among the normal young people. In 20 fiber bundles In the analysis of 100 node characteristics, it was found that the APOE e 3/ epsilon group was compared with the APOE 2/ E 3 group of bilateral thalamus radiation beams (left: t=2.839, p=0.007; right: t=4.174, p=0.000), and the corpus callosum (t=2.487, p=0.016; t=3.425,0.001) of the corpus callosum was low, and the value of the corpus callosum was lower than that of the 3 group. The right arch of the 3 group (t=: -2.958, p=0.018), the left upper longitudinal bundle (t=-2.737, p=0.025), the MD value of the hydrazine callosum (t=-3.208, p=0.008) was higher than the APOE epsilon 3 group, and the APOE 3/ epsilon 3 group of right buckle bands was higher than that of the 3 group, whereas the group of epsilon epsilon 3 in the left inferior frontal occipital fasciculus frontal lobe .011) and the right thalamus radiation beam (t=2.738, p=0.009) MD value was low. In further correlation analysis, it was found that the MD value of the right cingulate gyrus in the APOE e 2/ E 3 group was positively correlated with the comprehensive spatial navigation ability (r=0.829, p=0.042). Conclusion: the spatial navigation ability of the APOE risk gene carriers and non carriers was not found in the normal young people. However, the integrity of the fiber bundles in the APOE E 4 carriers was damaged. At the same time, the comprehensive spatial navigation ability of the APOE E 2 carriers was positively correlated with the integrity of the fiber bundle, suggesting that the APOE 4 gene may be one of the risk factors for the spatial navigation obstacle.
【学位授予单位】：南京大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R749.1;R445.2
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本文编号：2100425