背景成年哺乳動物海馬齒狀回的神經(jīng)干細(xì)胞能分化為神經(jīng)細(xì)胞稱為神經(jīng)發(fā)生。神經(jīng)發(fā)生過程主要包括干細(xì)胞增殖、前體細(xì)胞存活和分化、新生神經(jīng)元的成熟、突觸形成和神經(jīng)回路整合4個階段。這些新生神經(jīng)元具有與成熟顆粒細(xì)胞相似的結(jié)構(gòu)和功能特性,能與CA3區(qū)的錐體細(xì)胞建立突觸聯(lián)系,并產(chǎn)生突觸傳遞和誘發(fā)突觸可塑性。海馬的神經(jīng)發(fā)生也已被證明與空間認(rèn)知功能有關(guān)。因此,成年的神經(jīng)發(fā)生被認(rèn)為能取代和修復(fù)由于自然老化或病變造成的神經(jīng)元缺失,最大限度地維護腦的結(jié)構(gòu)和功能。阿爾茨海默�。ˋlzheimer’s disease, AD）是一種以進(jìn)行性認(rèn)知功能障礙為特征的神經(jīng)系統(tǒng)退行性疾病。新生神經(jīng)元是否能替代病變的神經(jīng)元,改善AD的認(rèn)知功能障礙已成為AD研究的一個新靶點。研究發(fā)現(xiàn),AD腦海馬的干細(xì)胞增殖有增加的趨勢,前體細(xì)胞向神經(jīng)元的分化比例明顯減少,同時新生神經(jīng)元的存活率顯著降低,并且新生神經(jīng)元的突起生長異常。這些研究都已證實,AD腦的神經(jīng)再生過程受到嚴(yán)重的損害,提示神經(jīng)再生障礙可能是AD認(rèn)知功能進(jìn)行性減退的重要病理機制之一。甾體激素脫氫表雄酮（Dehydroepiandrosterone, DHEA）及它的硫酸酯DHEA... 

【文章來源】：南京醫(yī)科大學(xué)江蘇省

【文章頁數(shù)】：80 頁

【學(xué)位級別】：碩士

【部分圖文】：

β25-35刺激神經(jīng)干細(xì)胞的增殖，但損害新生神經(jīng)細(xì)胞的存活EffectsofAβ25-35onprocessofadultneurogenesisinDG.Scalebars=100μm.Thewhitebarsindicatethedatafromcontrolmice.Theblackbarsindicatethedata23

圖 5 DHEA 能阻止 Aβ25-35損害新生神經(jīng)細(xì)胞的存活DHEA prevents Aβ-impaired survival of newborn neurons. The bar graph showthe mean density of 28-day-old BrdU+ cells from control mice (white barsAβ25-35-mice (black bars) and Aβ25-35-GOX mice (hatched bars). *P<0.05 an**P<0.01 vs. vehicle-treated mice; ##P<0.01 vs. control mice treated with DHEAEach group data contained 8 mice.27

0 DHEA激活σ1受體保護Aβ25-35小鼠海馬新生神經(jīng)元的下游分子PI3K和mActivation of PI3K and mTOR is required for DHEA-neuroprotection.K inhibitor U0126, the PI3K inhibitor LY294002, the PKC inhibitor chelerytthe mTOR inhibitor rapamycin was administered at 30 min before DHEA-injeBrdU-D6-12. The bar graph shows the mean density of 28-day-old BrdU+ <0.01 vs. Aβ25-35-mice treated with DHEA. Each group data contained 8 mic


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