Neuronal degeneration and glial cell-responses following trimethyltin intoxication in the rat
Neuronal degeneration and glial cell-responses following trimethyltin intoxication in the rat
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DOI：
10.1007/s00401-001-0505-5
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发表时间：
2002-06-01
影响因子：
12.7
通讯作者：
Ikeda, K
中科院分区：
文献类型：
--
作者：
Haga, S;Haga, C;Ikeda, K
三甲基锡（TMT）优先诱导海马和梨状皮层的神经元变化。在本研究中，我们研究了大鼠给予 TMT（腹腔注射 9 mg/kg 或 12 mg/kg 体重）后与神经变性相关的小胶质细胞和星形胶质细胞反应的时间过程。在 9 mg/kg TMT 的剂量下，使用 Gallyas-Braak (G-B) 浸渍方法，在第 4 天时，海马 CA1 和 CA3 区域中的神经变性被清楚地证明为嗜银（暗）神经元，该方法已被证明对神经变性具有敏感性和特异性。第 1 天，CA3 中的抗小胶质细胞反应因子 1 (MRF-1) 抗体通过免疫组织化学显示早期小胶质细胞反应，随后通过 G-B 方法进行形态学检测。第 2 天，通过神经胶质原纤维酸性蛋白 (GFAP) 的免疫组织化学染色显示星形胶质细胞的激活。与最大程度的神经变性同时，第 7 天，在 CA1 和 CA3 中观察到大量肥大的小胶质细胞和星形胶质细胞。通过 G-B 浸渍和 MRF-1 免疫组织化学的双重染色，退行性神经元的数量似乎与相邻小胶质细胞密切相关。到第 14 天，反应性小胶质细胞的数量显着减少到静息状态，而肥大的星形胶质细胞在 CA3 中仍然很突出，直到第 21 天。随着高剂量的 TMT，齿状回中的颗粒细胞以及 CA1 和 CA3 锥体细胞显着浸润。 TMT治疗后，伴随着神经退行性变，我们观察到小胶质细胞的早期反应和星形胶质细胞的延长激活，这表明神经胶质细胞在脑损伤后受损神经元的维持和修复中发挥着个体作用。
Trimethyltin (TMT) preferentially induces neuronal changes in the hippocampus and pyriform cortex. In the present study we investigated the time course of microglial and astroglial responses associated with neurodegeneration after the administration of TMT (i.p. 9 mg/kg or 12 mg/kg body weight) in the rat. At a dosage of 9 mg/kg TMT, neurodegeneration was clearly demonstrated in the CA1 and CA3 regions of the hippocampus as argyrophilic (dark) neurons by day 4 using the Gallyas-Braak (G-B) impregnation method that has been shown to be sensitive and specific for neurodegeneration. Early microglial response was immunohistochemically shown with anti-microglial response factor-1 (MRF-1) antibody in the CA3 by day 1, preceding neurodegeneration morphologically detected by the G-B method. Activation of astrocytes was revealed by immunohistochemical staining for glial fibrillary acidic protein (GFAP) by day 2. In parallel with the maximal neurodegeneration, large numbers of hypertrophied microglia and astrocytes were observed in the CA1 and CA3 by day 7. Numbers of degenerative neurons appeared to be closely associated with adjacent microglia by the double staining of G-B impregnation and MRF-1 immunohistochemistry. The number of reactive microglia considerably decreased to the resting state by day 14, while hypertrophied astrocytes were still prominent in the CA3 up to day 21. With the high dose of TMT, granule cells in the dentate gyrus and CA1 and CA3 pyramidal cells were significantly impregnated. After TMT treatment, accompaning neurodegeneration we observed early response of microglia and prolonged activation of astrocytes, suggesting an individual role of glial cells in maintenance and repair of damaged neurons following brain injury.