Department of Neuroscience, Kavli Institute for Neuroscience, Yale School of Medicine, Yale University, New Haven, CT 06510, USA.
Int J Mol Sci. 2023 Feb 23;24(5):4432. doi: 10.3390/ijms24054432.
Mitochondrial malfunction and morphologic disorganization have been observed in brain cells as part of complex pathological changes. However, it is unclear what may be the role of mitochondria in the initiation of pathologic processes or if mitochondrial disorders are consequences of earlier events. We analyzed the morphologic reorganization of organelles in an embryonic mouse brain during acute anoxia using an immunohistochemical identification of the disordered mitochondria, followed by electron microscopic three-dimensional (3D) reconstruction. We found swelling of the mitochondrial matrix after 3 h anoxia and probable dissociation of mitochondrial stomatin-like protein 2 (SLP2)-containing complexes after 4.5 h anoxia in the neocortex, hippocampus, and lateral ganglionic eminence. Surprisingly, deformation of the Golgi apparatus (GA) was detected already after 1 h of anoxia, when the mitochondria and other organelles still had a normal ultrastructure. The disordered GA showed concentrical swirling of the cisternae and formed spherical onion-like structures with the trans-cisterna in the center of the sphere. Such disturbance of the Golgi architecture likely interferes with its function for post-translational protein modification and secretory trafficking. Thus, the GA in embryonic mouse brain cells may be more vulnerable to anoxic conditions than the other organelles, including mitochondria.
在大脑细胞中观察到线粒体功能障碍和形态结构紊乱,这是复杂病理变化的一部分。然而,目前尚不清楚线粒体在病理过程的启动中可能扮演什么角色,或者线粒体紊乱是否是早期事件的结果。我们使用免疫组织化学方法鉴定紊乱的线粒体,然后进行电子显微镜三维(3D)重建,分析了胚胎期小鼠大脑在急性缺氧期间细胞器的形态重组。我们发现,在新皮层、海马体和外侧神经节隆起中,缺氧 3 小时后线粒体基质肿胀,缺氧 4.5 小时后可能分离出含有线粒体稳定素样蛋白 2(SLP2)的复合物。令人惊讶的是,在缺氧 1 小时时已经检测到高尔基体(GA)的变形,此时线粒体和其他细胞器仍具有正常的超微结构。紊乱的 GA 显示出 cisterna 的同心漩涡,并形成具有 trans-cisterna 位于球体中心的洋葱状球形结构。这种高尔基体结构的紊乱可能干扰其用于翻译后蛋白质修饰和分泌运输的功能。因此,胚胎期小鼠脑细胞中的 GA 可能比包括线粒体在内的其他细胞器对缺氧条件更为敏感。