Miller M W, Kuhn P E
Department of Psychiatry, University of Iowa College of Medicine, Iowa City 52242-1057, USA.
Brain Res. 1997 Sep 26;769(2):233-44. doi: 10.1016/s0006-8993(97)00713-0.
Neonatal lesion of the primary afferents in the infraorbital nerve causes the death of one-third of the neurons in the second-order target, the principal sensory nucleus of the trigeminal nerve (PSN). We examined the expression of two candidate 'death' proteins, p53 and the antigen recognized by the antibody ALZ-50, in the normal and deafferented PSN. In addition, the effect of neonatal transection of the infraorbital nerve (a major component of the trigeminal nerve) on protein expression was examined. The expression of c-fos in the developing PSN was also studied as an index of metabolic activity. Protein expression was measured using quantitative analyses of immunoblots and immunohistochemical preparations. The expression of p53- and ALZ-50-immunoreactivity in the normal PSN peaked during the first postnatal week. Transection of the infraorbital nerve directly affected the expression of p53 and the ALZ-50-positive antigen. The immunoblots showed that whereas p53 amounts were unaffected by the lesion, ALZ-50 expression was significantly upregulated in the ipsilateral PSN 2 h and 2 days postlesion. The density of p53- and ALZ-50-immunoreactive neurons was significantly higher in the ventral ipsilateral PSN (i.e., the target of the transected infraorbital nerve) than in the contralateral PSN. c-fos expression selectively and transiently rose in the ventral ipsilateral PSN within 2 h of the lesion. Thus, both p53 and the ALZ-50-positive antigen are involved in neuronal death. In light of data suggesting that ALZ-50 recognizes a phosphorylated form of p53, we conclude that neuronal death in the developing nervous system involves the post-translational modification of an existing protein, p53. The increase in ALZ-50 expression apparently occurs during a catabolic phase of neuronal death, as indicated by the increase in c-fos expression.
眶下神经中初级传入神经的新生期损伤会导致三叉神经主感觉核（PSN）这一二级靶区中三分之一的神经元死亡。我们检测了两种候选“死亡”蛋白——p53和被抗体ALZ - 50识别的抗原——在正常和去传入神经支配的PSN中的表达情况。此外，还研究了新生期切断眶下神经（三叉神经的主要组成部分）对蛋白表达的影响。同时，将发育中的PSN中c - fos的表达作为代谢活性指标进行了研究。通过对免疫印迹和免疫组织化学制剂的定量分析来测定蛋白表达。正常PSN中p53和ALZ - 50免疫反应性的表达在出生后第一周达到峰值。眶下神经切断术直接影响了p53和ALZ - 50阳性抗原的表达。免疫印迹显示，虽然p53的量不受损伤影响，但损伤后2小时和2天，同侧PSN中ALZ - 50的表达显著上调。同侧腹侧PSN（即切断的眶下神经的靶区）中p53和ALZ - 50免疫反应性神经元的密度显著高于对侧PSN。损伤后2小时内，同侧腹侧PSN中c - fos表达选择性且短暂地升高。因此，p53和ALZ - 50阳性抗原都与神经元死亡有关。鉴于有数据表明ALZ - 50识别p53的磷酸化形式，我们得出结论，发育中的神经系统中的神经元死亡涉及现有蛋白p53的翻译后修饰。如c - fos表达增加所示，ALZ - 50表达的增加显然发生在神经元死亡的分解代谢阶段。
