DNA甲基化(DNA methylation)是指在甲基轉(zhuǎn)移酶(DNA methyltransferases,DNMT)的催化下,在基因組CpG二核苷酸的胞嘧啶5’碳位共價(jià)鍵結(jié)合一個(gè)甲基基團(tuán),形成5-甲基胞嘧啶。DNA甲基化修飾改變了DNA的物理結(jié)構(gòu),阻止DNA結(jié)合蛋白在轉(zhuǎn)錄過(guò)程與DNA鏈的結(jié)合,從而調(diào)控基因表達(dá),是重要的表觀遺傳調(diào)節(jié)方式之一。DNA甲基化對(duì)營(yíng)養(yǎng)高度敏感,食物中的葉酸(folic acid,FA)、維生素B₁₂、甜菜堿(betaine)、甲硫氨酸(methionine)和膽堿(choline)等成分是重要的甲基供體,通過(guò)一碳單位代謝途徑直接或間接影響DNA甲基化。大量的流行病學(xué)統(tǒng)計(jì)數(shù)據(jù)和動(dòng)物研究表明圍孕期甲基供體營(yíng)養(yǎng)素的不足或過(guò)剩,可通過(guò)影響DNA甲基化等表觀遺傳修飾,改變部分關(guān)鍵基因的表達(dá),從而引起子代多種神經(jīng)發(fā)育、行為和神經(jīng)認(rèn)知功能等表型的改變。但上述的研究幾乎都集中在母體因素,缺乏對(duì)父系甲基供體攝取對(duì)子代影響的考察。已有研究證據(jù)表明,精子細(xì)胞的表觀基因組會(huì)受到父親環(huán)境暴露因素的影響,從而引發(fā)子代表型的改變,所以為了探討父親高甲基化飲食暴露對(duì)子...

【文章頁(yè)數(shù)】：88 頁(yè)

【學(xué)位級(jí)別】：博士

【部分圖文】：

圖1MDF1小鼠表現(xiàn)出海馬依賴性學(xué)習(xí)和記憶受損Figure1Impairedhippocampus-dependentlearningandmemoryinMDF1offspringmice(A)Experimentaldesign.(B)InMWM,twogroups(n=8micepergroup)tookthesametimeinfindinghiddenplatforms(two-wayrepeated-measureANOVAwithbetween-subjectsfactorsgenotypeandtime;Sidak’smultiplecomparisonstest,p>0.05inalllatencycomparisonsbetweentwogroups).

青島大學(xué)博士學(xué)位論文礙。

圖2MDF1小鼠海馬腦電的θ振蕩波減少Fig2AlteredthetaoscillationsinMDF1mice(A)RepresentativetimefrequencyplotsshowreducedtypicalthetasegmentsinaMDF1mouse(below)

青島大學(xué)博士學(xué)位論文30圖2MDF1小鼠海馬腦電的θ振蕩波減少Fig2AlteredthetaoscillationsinMDF1mice(A)RepresentativetimefrequencyplotsshowreducedtypicalthetasegmentsinaMD....

圖3場(chǎng)電位記錄MDF1小鼠海馬SC-CA1通路基本突觸傳遞正常而LTP受損Fig3Fieldpotentialrecordingshowsimpairedhippocampallong-termpotentiationinMDF1mice(A)TheschematicdiagramofSchaffer-CA1pathwayandthelocationofthestimulatingelectrodeandrecordingelectrode.(B)ThephotoofSchaffer-CA1pathwayandthelocationofthestimulatingelectrodeandrecordingelectrode.Theinput-outputcurve(C)andpaired-pulseratio(PPR)(D)indicat

青島大學(xué)博士學(xué)位論文32圖3場(chǎng)電位記錄MDF1小鼠海馬SC-CA1通路基本突觸傳遞正常而LTP受損Fig3Fieldpotentialrecordingshowsimpairedhippocampallong-termpotentiationinMDF1mice(A)Thesch....

圖4MDF1小鼠海馬CA1區(qū)錐體神經(jīng)元內(nèi)在興奮性降低Fig4DifferentintrinsicexcitabilityofCA1pyramidalneuronsintheMDF1micecomparedtotheCDF1mice.(A)Samplerecordingsshowingactionpotentialsevokedbyadepolarizingcurrentinjection.Upper:the

青島大學(xué)博士學(xué)位論文34圖4MDF1小鼠海馬CA1區(qū)錐體神經(jīng)元內(nèi)在興奮性降低Fig4DifferentintrinsicexcitabilityofCA1pyramidalneuronsintheMDF1micecomparedtotheCDF1mice.(A)Samplerec....

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