褪黑素对成年大鼠脑细胞的影响及其与学习记忆的关系

发布时间：2018-11-25 22:34

【摘要】：目的: 探讨褪黑素对成年脑神经干细胞、星形胶质细胞的影响及其与学习记忆的关系。方法: 建立去松果体及褪黑素替代的成年SD 大鼠模型,用免疫组织化学方法计数侧脑室室管膜下区(SVZ)和齿状回颗粒细胞下层(SGZ)的增殖细胞核抗原(PCNA)阳性细胞数以及海马、基底前脑、尾壳核和扣带前皮质的胶质原纤维酸性蛋白(GFAP)阳性细胞数,并用Morris 水迷宫测定大鼠的学习记忆能力。结果: 去松果体可使大鼠SVZ 和SGZ 的PCNA 细胞数、海马和基底前脑的GFAP 阳性细胞数以及学习记忆能力明显下降(P0.01);用20ug/kg 或200ug/kg 剂量的褪黑素替代治疗,可使上述指标明显上升(P0.01),并接近正常水平。然而,用2mg/kg 剂量的褪黑素替代治疗则使以上各指标明显下降至去松果体大鼠的水平。不论去松果体还是褪黑素替代对尾壳核及扣带前皮质的GFAP 阳性细胞数均无明显影响(P 0.05)。结论: 用适宜剂量的褪黑素替代治疗对成年神经干细胞增殖、星形胶质细胞增殖及学习记忆能力均有相似的促进作用,提示褪黑素对学习记忆的影响是通过作用于神经干细胞和星形胶质细胞上的相应受体实现的。用过高剂量的褪黑素替代治疗对上述各指标具有抑制作用。褪黑素对尾壳核及扣带前皮质的星形胶质细胞无明显的影响可能与这两个脑区缺乏褪黑素受体有关。这些结果为阐明学习记忆的神经内分泌机制以及调动自体内源性神经干细胞治疗老年性痴呆提供了新的线索和资料。
[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.
【学位授予单位】：广西医科大学
【学位级别】：硕士
【学位授予年份】：2005
【分类号】：R33

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