Changes in APP, PS1 and other factors related to Alzheimer's disease pathophysiology after trimethyltin-induced brain lesion in the rat
Changes in APP, PS1 and other factors related to Alzheimer's disease pathophysiology after trimethyltin-induced brain lesion in the rat
复制标题
DOI：
10.1080/1029842021000045471
复制
发表时间：
2002-01-01
影响因子：
3.7
通讯作者：
Luthman, Johan
中科院分区：
文献类型：
--
作者：
Nilsberth, Camilla;Kostyszyn, Beata;Luthman, Johan
氯化三甲基锡（TMT）诱导边缘系统神经变性，导致行为改变，包括认知缺陷。本实验通过对SD大鼠进行TMT损伤，研究了与阿尔茨海默病（AD）相关的各种因素。在单次TMT注射（7 mg/kg i. p.）TMT处理后，海马CA 3区锥体神经元广泛变性，同时伴有CA 1区外层、肠皮质和梨状皮质Ⅱ层神经元变性。受影响的地区表现出丰富的浓缩嗜酸性和TUNEL阳性神经元细胞，这是明显的TMT后第4天，增加到第7天，随后消失。在受影响的区域，APP 695 mRNA的水平在注射TMT后随时间逐渐下降。虽然APP-KPI或PS1 mRNA的总体表达没有明显变化，但对CA 3c区域的详细分析表明，mRNA表达从神经元转移到神经胶质细胞。三天后TMT，梨状皮质，CA 3区和DG的神经元表达高水平的c-fos mRNA，缓慢下降，成为正常化时，在第28天进行分析。在TMT后第7天，在CA 3c区观察到一些表达IL-1 β mRNA的胶质细胞，因此，TMT暴露导致边缘系统中APP、APP-KPI、PS1、c-fos和IL-1 β表达的改变。这些结果表明，TMT病变，不仅共享某些关键特征的AD的病理学和区域神经退行性变，但也诱导的重要因素相关的AD的病理生理。
Trimethyltin (TMT) chloride induces limbic system neurodegeneration, resulting in behavioral alterations including cognitive deficits. Different factors related to Alzheimer's disease (AD) were studied after TMT lesion in Sprague-Dawley rats. The expression of amyloid precursor protein (APP) containing 695 amino acids (APP695), APP containing the Kuniz protease inhibitor domain (APP-KPI), presenilin 1 (PS1), c-fos and IL-1 beta was investigated at different timepoints after a single TMT injection (7 mg/kg i.p.) using in situ hybridization and immunohistochemistry.After the TMT treatment, extensive degeneration of pyramidal neurons was observed in the CA3 region of the hippocampus, concomitant with neurodegeneration in the outer layer of the CA1 region and layer II of enterhinal and piriform cortex. The affected regions showed abundant condensed eosinophilic and TUNEL-positive neuronal cells, that were apparent at day 4 after TMT, increasing to day 7 and subsequently disappearing. In the affected regions the levels of APP695 mRNA gradually declined with time after the TMT injection. While there was no apparent alteration in the overall expression of APP-KPI or PS1 mRNA, detailed analysis of the CA3c region showed that the mRNA expression shifted from neurons to glial cells. Three days after TMT, neurons in the piriform cortex, the CA3 region and DG expressed high levels of c-fos mRNA that slowly declined to become normalized when analyzed at day 28. At day 7 after TMT a few distinct IL-1 beta mRNA expressing glial cells were observed in the CA3c region.Thus, TMT exposure leads to alterations in the expression of APP, APP-KPI, PS1, c-fos and IL-1 beta in the limbic system. These findings suggest that TMT lesions, not only share certain key features of AD symptomatology and regional neurodegeneration, but also induce effects on important factors related to the pathophysiology of AD.