Apoptosis in experimental cerebral malaria: spatial profile of cleaved caspase-3 and ultrastructural alterations in different disease stages
Apoptosis in experimental cerebral malaria: spatial profile of cleaved caspase-3 and ultrastructural alterations in different disease stages
复制标题
DOI：
10.1111/j.1365-2990.2007.00833.x
复制
发表时间：
2007-10-01
影响因子：
5
通讯作者：
Beer, R.
中科院分区：
文献类型：
--
作者：
Lackner, P.;Burger, C.;Beer, R.
脑疟疾与高死亡率和发病率相关，因为一定比例的幸存者患有持续的神经系统后遗症。导致死亡和功能障碍的机制尚不完全清楚。本研究研究了伯氏疟原虫感染小鼠脑内细胞凋亡的生化和形态学标志物。Cleaved caspase-3在有CM临床症状的动物大脑中检测到，免疫反应性与疾病的临床严重程度直接相关。脑尾部对裂解caspase-3表现出更强的免疫反应性。双标记实验显示caspase-3主要在神经元和少突胶质细胞中加工。这些细胞在超微结构分析中也表现出凋亡样的形态特征。此外，在内皮细胞中发现了caspase-3的裂解。与神经元和少突胶质细胞不同，内皮细胞的凋亡在疾病的早期阶段就已经发生。我们的结果首次证明了caspase-3在CM动物的不同中枢神经系统细胞中的加工。在小鼠模型中，内皮细胞的凋亡可能是疾病发展的关键问题。神经系统体征和症状可能至少部分归因于小鼠CM晚期神经元和神经胶质细胞的凋亡变性。
Cerebral malaria (CM) is associated with high mortality and morbidity as a certain percentage of survivors suffers from persistent neurological sequelae. The mechanisms leading to death and functional impairments are yet not fully understood. This study investigated biochemical and morphological markers of apoptosis in the brains of mice infected with Plasmodium berghei ANKA. Cleaved caspase-3 was detected in the brains of animals with clinical signs of CM and immunoreactivity directly correlated with the clinical severity of the disease. Caudal parts of the brain showed more intense immunoreactivity for cleaved caspase-3. Double-labelling experiments revealed processing of caspase-3 primarily in neurons and oligodendrocytes. These cells also exhibited apoptotic-like morphological profiles in ultrastructural analysis. Further, cleavage of caspase-3 was found in endothelial cells. In contrast to neurons and oligodendrocytes, apoptosis of endothelial cells already occurred in early stages of the disease. Our results are the first to demonstrate processing of caspase-3 in different central nervous system cells of animals with CM. Apoptosis of endothelial cells may represent a critical issue for the development of the disease in the mouse model. Neurological signs and symptoms might be attributable, at least in part, to apoptotic degeneration of neurons and glia in advanced stages of murine CM.