Messina A, Jaworowski A, Bell C
Department of Physiology, Melbourne University, Royal Melbourne Hospital, Royal Parade Parkville, Australia.
J Comp Neurol. 1996 Sep 2;372(4):544-50. doi: 10.1002/(SICI)1096-9861(19960902)372:4<544::AID-CNE4>3.0.CO;2-4.
A large proportion of neurons die during normal development of the nervous system via an active process known as apoptosis. We counted the total number of neurons and apoptotic neurons in the superior cervical ganglion of the GH Wistar rat strain, which possesses a neurotrophic deficit leading to excessive perinatal cell death, and in its normal counterpart (N) by using the optical disector method to quantify the extent of apoptosis during postnatal development. Total neuron numbers fell between postnatal days 3 and 14 by 10 and 40% in N and GH, respectively. In GH ganglia, 1.5% of neurons were apoptotic at any given time, as determined by the presence of condensed chromatin clumps. Some types of cell death have been associated with expression of the immediate-early genes c-fos and c-jun. Therefore, we used histological and immunocytochemical techniques to characterise individual neurons and to detect the products of these immediate-early genes during developmental cell death. All apoptotic cells were immunopositive for c-jun protein, whereas no c-jun protein was detected in nonapoptotic cells. Conversely, members of the fos family of transcription factors were detected in the nucleus of 60% of nonapoptotic cells but in only a minor proportion of cells undergoing apoptosis. These results indicate that c-jun occurs in neurons that are committed to die. This is the first situation in which the presence of jun protein has been correlated with normal programmed cell death in individual apoptotic neurons.
在神经系统的正常发育过程中,很大一部分神经元会通过一种称为凋亡的主动过程死亡。我们使用光学分割法来量化出生后发育过程中凋亡的程度,统计了GH Wistar大鼠品系颈上神经节中的神经元总数和凋亡神经元数量,该品系存在神经营养缺陷,导致围产期细胞过度死亡,同时也统计了其正常对应品系(N)中的上述数据。在出生后第3天到第14天之间,N品系和GH品系的神经元总数分别下降了10%和40%。在GH神经节中,通过存在浓缩染色质团块确定,在任何给定时间有1.5%的神经元发生凋亡。某些类型的细胞死亡与即早基因c-fos和c-jun的表达有关。因此,我们使用组织学和免疫细胞化学技术来表征单个神经元,并在发育性细胞死亡期间检测这些即早基因的产物。所有凋亡细胞对c-jun蛋白呈免疫阳性,而在非凋亡细胞中未检测到c-jun蛋白。相反,在60%的非凋亡细胞的细胞核中检测到转录因子fos家族的成员,但仅在一小部分正在凋亡的细胞中检测到。这些结果表明,c-jun存在于注定死亡的神经元中。这是首次发现jun蛋白的存在与单个凋亡神经元中的正常程序性细胞死亡相关的情况。