Koliatsos V E, Applegate M D, Kitt C A, Walker L C, DeLong M R, Price D L
Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 21205-2182.
Brain Res. 1989 Mar 20;482(2):205-18. doi: 10.1016/0006-8993(89)91183-9.
Lesions of the fimbria-fornix (FF) have been reported to cause retrograde changes in neurons of the medial septal nucleus (MSN). To analyze the nature and time course of these events, we investigated changes in cytoskeletal elements (phosphorylated and non-phosphorylated neurofilament (NF) proteins) and transmitter-related enzymes (choline acetyltransferase (ChAT) in MSN neurons following FF transection. During the first week postlesion, ChAT immunoreactivity and size of many perikarya were reduced. Irregular, swollen cholinergic fibers appeared first at postlesion day 2 in caudal septum and soon spread rostrally, reaching rostral septum by day 7. A few perikarya developed abnormal accumulations of phosphorylated NFs. At postlesion days 7-10, many neurons did not stain for ChAT. Phosphorylated NFs were present in many perikarya. At this time, cell loss was apparent in Nissl-stained material. Cholinergic cell loss continued through postlesion weeks 6-8 but at a much slower rate than during the first week. Phosphorylated NF accumulations in MSN perikarya persisted until postlesion week 6, disappearing thereafter. Double-immunostaining procedures showed that MSN neurons expressed both ChAT and phosphorylated NF immunoreactivity at postlesion day 3; however, at days 7 and 14, cells that accumulated phosphorylated NFs did not stain for ChAT. The results of this study indicate that FF transection leads to perikaryal shrinkage with loss of ChAT immunoreactivity, perikaryal phosphorylation of NFs, cholinergic fiber abnormalities, and cell loss. Recent evidence suggests that reduction of transmitter markers and aberrant phosphorylation of NFs may be involved in the pathogenesis of several neurodegenerative disorders, including Alzheimer's disease. Therefore, FF transection provides a useful animal model for further investigations of complex disorders of the central nervous system that involve degeneration of transmitter-specific pathways.
据报道，穹窿 - 穹窿海马伞（FF）损伤会导致内侧隔核（MSN）神经元发生逆行性变化。为了分析这些事件的性质和时间进程，我们研究了FF横断后MSN神经元中细胞骨架成分（磷酸化和非磷酸化神经丝（NF）蛋白）以及与递质相关的酶（胆碱乙酰转移酶（ChAT））的变化。在损伤后的第一周，许多胞体的ChAT免疫反应性和大小降低。不规则、肿胀的胆碱能纤维在损伤后第2天首先出现在尾侧隔区，随后迅速向头侧扩散，到第7天到达头侧隔区。一些胞体出现磷酸化NF的异常积聚。在损伤后第7 - 10天，许多神经元ChAT染色阴性。许多胞体中存在磷酸化NF。此时，尼氏染色材料中可见明显的细胞丢失。胆碱能细胞丢失在损伤后第6 - 8周持续存在，但速度比第一周慢得多。MSN胞体中磷酸化NF的积聚一直持续到损伤后第6周，此后消失。双重免疫染色程序显示，在损伤后第3天，MSN神经元同时表达ChAT和磷酸化NF免疫反应性；然而，在第7天和第14天，积聚磷酸化NF的细胞ChAT染色阴性。本研究结果表明，FF横断导致胞体萎缩，ChAT免疫反应性丧失，NF的胞体磷酸化，胆碱能纤维异常以及细胞丢失。最近的证据表明，递质标志物的减少和NF的异常磷酸化可能参与包括阿尔茨海默病在内的几种神经退行性疾病的发病机制。因此，FF横断为进一步研究涉及递质特异性通路退化的中枢神经系统复杂疾病提供了一个有用的动物模型。
