【摘要】：目的: 探討褪黑素對(duì)成年腦神經(jīng)干細(xì)胞、星形膠質(zhì)細(xì)胞的影響及其與學(xué)習(xí)記憶的關(guān)系。方法: 建立去松果體及褪黑素替代的成年SD 大鼠模型,用免疫組織化學(xué)方法計(jì)數(shù)側(cè)腦室室管膜下區(qū)(SVZ)和齒狀回顆粒細(xì)胞下層(SGZ)的增殖細(xì)胞核抗原(PCNA)陽(yáng)性細(xì)胞數(shù)以及海馬、基底前腦、尾殼核和扣帶前皮質(zhì)的膠質(zhì)原纖維酸性蛋白(GFAP)陽(yáng)性細(xì)胞數(shù),并用Morris 水迷宮測(cè)定大鼠的學(xué)習(xí)記憶能力。結(jié)果: 去松果體可使大鼠SVZ 和SGZ 的PCNA 細(xì)胞數(shù)、海馬和基底前腦的GFAP 陽(yáng)性細(xì)胞數(shù)以及學(xué)習(xí)記憶能力明顯下降(P0.01);用20ug/kg 或200ug/kg 劑量的褪黑素替代治療,可使上述指標(biāo)明顯上升(P0.01),并接近正常水平。然而,用2mg/kg 劑量的褪黑素替代治療則使以上各指標(biāo)明顯下降至去松果體大鼠的水平。不論去松果體還是褪黑素替代對(duì)尾殼核及扣帶前皮質(zhì)的GFAP 陽(yáng)性細(xì)胞數(shù)均無(wú)明顯影響(P 0.05)。結(jié)論: 用適宜劑量的褪黑素替代治療對(duì)成年神經(jīng)干細(xì)胞增殖、星形膠質(zhì)細(xì)胞增殖及學(xué)習(xí)記憶能力均有相似的促進(jìn)作用,提示褪黑素對(duì)學(xué)習(xí)記憶的影響是通過(guò)作用于神經(jīng)干細(xì)胞和星形膠質(zhì)細(xì)胞上的相應(yīng)受體實(shí)現(xiàn)的。用過(guò)高劑量的褪黑素替代治療對(duì)上述各指標(biāo)具有抑制作用。褪黑素對(duì)尾殼核及扣帶前皮質(zhì)的星形膠質(zhì)細(xì)胞無(wú)明顯的影響可能與這兩個(gè)腦區(qū)缺乏褪黑素受體有關(guān)。這些結(jié)果為闡明學(xué)習(xí)記憶的神經(jīng)內(nèi)分泌機(jī)制以及調(diào)動(dòng)自體內(nèi)源性神經(jīng)干細(xì)胞治療老年性癡呆提供了新的線(xiàn)索和資料。
[Abstract]:Aim: to investigate the effect of melatonin on adult neural stem cells and astrocytes and its relationship with learning and memory. Methods: the model of pinealectomy and melatonin replacement in adult SD rats was established. The number of proliferating cell nuclear antigen (PCNA) positive cells in subependymal area of lateral ventricle and (SGZ) in subgranular cell of dentate gyrus and hippocampus and basal forebrain were counted by immunohistochemical method. The number of (GFAP) positive cells of glial fibrillary acidic protein (GFAP) in caudate putamen and cingulate precortex was measured by Morris water maze. Results: the number of PCNA cells in SVZ and SGZ, the number of GFAP positive cells in hippocampus and basal forebrain and the ability of learning and memory were significantly decreased after pinealectomy (P0.01). Melatonin replacement therapy with 20ug/kg or 200ug/kg could significantly increase the above indexes (P0.01) and approach the normal level. However, melatonin replacement therapy with 2mg/kg dose significantly reduced the above indexes to the level of pinealectomy rats. Both pinealectomy and melatonin replacement had no significant effect on the number of GFAP positive cells in caudate putamen and cingulate precortex (P0. 05). Conclusion: melatonin replacement therapy has similar effects on the proliferation of adult neural stem cells, astrocyte proliferation and learning and memory ability. The results suggest that the effect of melatonin on learning and memory is achieved by acting on the corresponding receptors on neural stem cells and astrocytes. Too high dose of melatonin replacement therapy can inhibit the above indexes. No effect of melatonin on astrocytes in caudate putamen nucleus and cingulate precortex may be related to the absence of melatonin receptor in these two brain regions. These results provide new clues and data for elucidating the neuroendocrine mechanism of learning and memory and mobilizing autogenous neural stem cells in the treatment of Alzheimer's disease.
【學(xué)位授予單位】：廣西醫(yī)科大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2005
【分類(lèi)號(hào)】：R33

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