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APOE風(fēng)險(xiǎn)基因和性別差異對(duì)空間導(dǎo)航能力相關(guān)腦結(jié)構(gòu)的影響

發(fā)布時(shí)間:2018-07-05 13:53

  本文選題:空間導(dǎo)航 + 性別 ; 參考:《南京大學(xué)》2017年碩士論文


【摘要】:第一部分空間導(dǎo)航能力與海馬亞區(qū)體積相關(guān)性的性別差異化研究目的:空間導(dǎo)航能力是一種非常重要的基本生活能力,包含了多個(gè)復(fù)雜的認(rèn)知及感知過(guò)程,其能力受損與萎縮的海馬體積明顯相關(guān)。前人報(bào)道,性別不同所引起的空間導(dǎo)航行為學(xué)不同,但是這種差異的腦結(jié)構(gòu)改變基礎(chǔ)還不是很明確。本研究旨在研究正常年輕人中,性別對(duì)其空間導(dǎo)航能力的影響,以及其與海馬體積、海馬亞區(qū)體積的聯(lián)系。材料與方法:通過(guò)志愿者招募流程,收入63名正常年輕志愿者納入本研究(男33名,年齡24.00±1.27歲;女30名,年齡23.90±1.95歲)。所有被試者均進(jìn)行了空間導(dǎo)航測(cè)試及頭顱磁共振檢查?臻g導(dǎo)航測(cè)試使用PC版的隱藏任務(wù)測(cè)試(Hidden Goal Task,HGT),即視覺(jué)模擬的水迷宮(Morris Water Maze,MWM)測(cè)試進(jìn)行,分別測(cè)試綜合導(dǎo)航、環(huán)境導(dǎo)航、自我導(dǎo)航及延遲-環(huán)境導(dǎo)航能力;采用3D-T1加權(quán)成像序列進(jìn)行顱腦高清結(jié)構(gòu)像采集,并通過(guò)FreeSurfer軟件分割及計(jì)算得到每個(gè)被試雙側(cè)海馬亞區(qū)和海馬整體的體積,FreeSurfer5.3.0將海馬分為CA1、CA2_3、CA4_DG、下托(subiculum)、前下托(presubiculum)、海馬裂(fissure)、海馬傘(fimbria)以及無(wú)法分割的尾區(qū)(標(biāo)記為hippocampus)8個(gè)亞區(qū)。全部受試者按照性別分為兩組。利用兩個(gè)獨(dú)立樣本T檢驗(yàn)(two sample t test)對(duì)兩組的各種空間導(dǎo)航能力、年齡、受教育程度做組間比較。用Pearson相關(guān)檢驗(yàn)和偏相關(guān)檢驗(yàn)對(duì)空間導(dǎo)航能力值與海馬體積與海馬亞區(qū)體積進(jìn)行分析。結(jié)果:研究發(fā)現(xiàn)在正常年輕人中男性的綜合空間導(dǎo)航能力較女性的差(男性:28.69±16.59;女性:22.33±6.27;p=0.047),兩組的自我導(dǎo)航和環(huán)境導(dǎo)航比較沒(méi)有統(tǒng)計(jì)學(xué)差異。在相關(guān)分析中發(fā)現(xiàn),綜合導(dǎo)航能力的差異與右側(cè)海馬前下托(r=0.313,p=0.013)和下托(r=0.262,p=0.040)的體積變化有關(guān)。結(jié)論:在健康年輕人中,男女的綜合空間導(dǎo)航能力有差異,且這種差異與右側(cè)海馬前下托與下托的體積差異相關(guān)。這一研究強(qiáng)調(diào)了空間導(dǎo)航能力與海馬亞區(qū)之間的關(guān)系,提示不同的海馬亞區(qū)在空間導(dǎo)航中的不同作用,為下一步揭示空間導(dǎo)航差異的結(jié)構(gòu)與功能基礎(chǔ)打下了基礎(chǔ)。第二部分APOE風(fēng)險(xiǎn)基因攜帶者中空間導(dǎo)航能力和腦白質(zhì)纖維束特征的相關(guān)性研究目的:APOE ε4等位基因被認(rèn)為是阿爾茨海默病(Alzheimer's disease,AD)的一個(gè)主要危險(xiǎn)基因,空間導(dǎo)航能力受損及纖維束完整性受到破壞在老年人和AD患者中也非常常見(jiàn)。然而空間導(dǎo)航能力受損與纖維束完整性在APOE風(fēng)險(xiǎn)基因攜帶者中的相關(guān)性還不甚明確。本文旨在研究正常年輕人中APOE風(fēng)險(xiǎn)基因攜帶者中空間導(dǎo)航能力和纖維束特征的相關(guān)性。材料與方法:通過(guò)前章所述的志愿者招募流程及空間導(dǎo)航測(cè)試和頭顱磁共振檢查的60名被試抽取外周血進(jìn)行基因型檢測(cè)。用纖維束自動(dòng)定量分析法(automating fiber-tract quantification,AFQ)分析腦內(nèi) 20 條纖維束上各 100 個(gè)節(jié)點(diǎn)的各向異性分?jǐn)?shù)(fractional anisotropy,FA)和平均擴(kuò)散系數(shù)(mean diffusivity,MD)。全部受試者按照基因型分為三組。單因素方差分析和spearman相關(guān)檢驗(yàn)分別用于對(duì)三組的空間導(dǎo)航能力、20條纖維束上的彌散張量指標(biāo)做組間比較和相關(guān)性分析。結(jié)果:綜合導(dǎo)航能力(p=0.627),自我導(dǎo)航能力(p=0.768)及環(huán)境導(dǎo)航能力(p=0.491)在三組APOE等位基因型(ε2/ε3、ε3/ε3、ε4/ε3)正常年輕人中均不存在組間顯著差異。在20條纖維束的100個(gè)節(jié)點(diǎn)特征分析中發(fā)現(xiàn),APOE ε3/ε3組較APOE ε2/ε3組的雙側(cè)丘腦輻射束(左側(cè):t=2.839,p=0.007;右側(cè):t=4.174,p=0.000)、胼胝體(膝部:t=2.487,p=0.016;壓部:t=3.425,0.001)的 FA 值低,APOEε4/ε3 組較 APOEε2/ε3 組的胼胝體(壓部:t=2.350,p=0.039)的 FA 值低。APOE ε4/ε3 組右側(cè)弓形束(t=:-2.958,p=0.018)、左側(cè)上縱束(t=-2.737,p=0.025)、肼胝體(壓部:t=-3.208,p=0.008)MD 值較 APOEε2ε3 組高;APOEε3/ε3 組右側(cè)扣帶束(t=-3.211,p=0.002)MD 值較 APOE ε2/ε3 組高;而 APOE ε3/ε3 組較APOEε2/ε3組在左側(cè)下額枕束額葉段(t=2.656,p=0.011)及右側(cè)丘腦輻射束(t=2.738,p=0.009)MD值為低。在進(jìn)一步的相關(guān)分析中發(fā)現(xiàn):APOEε2/ε3組中右側(cè)扣帶束扣帶回MD值與綜合空間導(dǎo)航能力正相關(guān)(r=0.829,p=0.042)。結(jié)論:在正常年輕人中,APOE風(fēng)險(xiǎn)基因攜帶者與非攜帶者的空間導(dǎo)航能力未發(fā)現(xiàn)顯著差異,但APOEε4攜帶者中纖維束完整性出現(xiàn)破壞。同時(shí),APOEε2攜帶者中綜合空間導(dǎo)航能力與纖維束完整性呈現(xiàn)正相關(guān),提示APOE ε4基因可能是空間導(dǎo)航障礙的風(fēng)險(xiǎn)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.
【學(xué)位授予單位】:南京大學(xué)
【學(xué)位級(jí)別】:碩士
【學(xué)位授予年份】:2017
【分類(lèi)號(hào)】:R749.1;R445.2
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本文編號(hào):2100425

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