Fukuda T, Wang H, Nakanishi H, Yamamoto K, Kosaka T
Department of Anatomy and Neurobiology, Faculty of Medicine, Kyushu University, Fukuoka, Japan.
Neurosci Res. 1999 Jan;33(1):49-55. doi: 10.1016/s0168-0102(98)00111-4.
Apoptosis has been recently implicated in the dying process of neurons under several pathological conditions including ischemia. However, although apoptosis was originally defined on the basis of its unique ultrastructural features (Kerr et al., 1972. Br. J. Cancer 26, 239-257; Wyllie et al., 1980. Int. Rev. Cytol. 68, 251-306), unambiguous ultrastructural evidence of apoptosis has been rarely demonstrated in the adult brain. In this study, we examined ultrastructural changes in mouse hippocampal neurons after transient hypoxic-ischemia. A small population of dentate granule cells showed typical apoptotic ultrastructures that could be used as internal morphological standards of apoptosis, whereas most other hippocampal neurons consistently showed a distinct form of cellular disintegration. Nuclei of the latter cells shrank and became TUNEL-positive but were distinguishable from apoptotic nuclei by both the presence of characteristic reticular-formed chromatin condensation and the absence of nuclear fragmentation. Perikarya of degenerating neurons also shrank as in apoptosis, but apoptotic bodies were not observed. Although organelles other than mitochondria disappeared almost completely from the perikarya, neither plasma nor mitochondrial membranes were disrupted, indicating that these changes were also different from typical necrosis. The presence of a novel form of cell death suggests the necessity of morphological re-examination of neuronal death, particularly in mature neurons in vivo.
最近，细胞凋亡被认为参与了包括缺血在内的几种病理条件下神经元的死亡过程。然而，尽管细胞凋亡最初是根据其独特的超微结构特征来定义的（Kerr等人，1972年。《英国癌症杂志》26卷，239 - 257页；Wyllie等人，1980年。《细胞生物学国际评论》68卷，251 - 306页），但在成人大脑中很少有明确的细胞凋亡超微结构证据被证实。在本研究中，我们检测了短暂缺氧缺血后小鼠海马神经元的超微结构变化。一小部分齿状颗粒细胞呈现出典型的凋亡超微结构，可作为细胞凋亡的内部形态学标准，而大多数其他海马神经元则持续呈现出一种独特的细胞解体形式。后一种细胞的细胞核缩小并呈TUNEL阳性，但通过特征性的网状染色质凝聚的存在和核碎裂的缺失，可与凋亡细胞核区分开来。退化神经元的胞体也如细胞凋亡时一样缩小，但未观察到凋亡小体。尽管除线粒体之外的细胞器几乎完全从胞体中消失，但质膜和线粒体膜均未破裂，这表明这些变化也不同于典型的坏死。一种新型细胞死亡形式的存在表明有必要对神经元死亡进行形态学重新检查，特别是在体内成熟神经元中。
