Fischer W, Björklund A
Department of Medical Cell Research, University of Lund, Sweden.
Exp Neurol. 1991 Aug;113(2):93-108. doi: 10.1016/0014-4886(91)90167-b.
The time course of cellular changes in the medial septum (MS) and vertical limb of the diagonal band area (VDB) after a complete unilateral fimbria-fornix (FF) transection has been studied using prelabeling of the septohippocampal neurons by bilateral hippocampal injections of the fluorescent retrograde tracer Fluoro-Gold (FG), in combination with acetylcholine esterase (AChE) histochemistry and nerve growth factor receptor (NGFr) immunocytochemistry. The results show that the long-term disappearance of AChE-positive and NGFr-positive cells represents a combination of down-regulation of the marker proteins, cell shrinkage, and an actual cell loss. By 4 weeks after lesion the loss of FG-prelabeled cells amounted to 50% in MS and 30% in VDB. A further 25-30% of the MS neurons survived (as indicated by the presence of FG label), but were undetectable by the AChE and NGFr markers. Down-regulation of the marker proteins and cell shrinkage preceded the cell loss by more than a week: while shrinkage and reduced numbers of AChE/NGFr positive cells was evident already by 4-7 days, an actual cell loss (i.e., loss of FG-prelabeled cells) became evident only at 4 weeks after lesion. Continuous intraventricular NGF infusion (0.15 micrograms/day) was capable of counteracting all three types of changes. Infusion over 2 weeks reversed both atrophy and loss of AChE/NGFr staining, whereas infusion over 4 weeks completely prevented the later occurring cell loss. In addition, the NGF infusions induced significant hypertrophy in the undamaged cholinergic neurons in both nucleus basalis and striatum. It is concluded that down-regulation of marker proteins, such as AChE and NGFr, and cellular atrophy precede cell death in the axotomized septohippocampal system and that about 1/3 of the axotomized septal cholinergic neurons may survive for a long time in a down-regulated atrophic state. Exogenous NGF can prevent both the atrophic and the degenerative processes.
采用双侧海马注射荧光逆行示踪剂氟金（FG）对海马-隔区神经元进行预标记，并结合乙酰胆碱酯酶（AChE）组织化学和神经生长因子受体（NGFr）免疫细胞化学技术，研究了完全性单侧穹窿-海马伞（FF）横断术后内侧隔区（MS）和斜角带垂直支区域（VDB）细胞变化的时间进程。结果表明，AChE阳性和NGFr阳性细胞的长期消失是标记蛋白下调、细胞萎缩和实际细胞丢失共同作用的结果。损伤后4周，MS区FG预标记细胞丢失达50%，VDB区为30%。另有25%-30%的MS神经元存活（以FG标记的存在为指标），但AChE和NGFr标记无法检测到。标记蛋白的下调和细胞萎缩比细胞丢失提前一周以上：虽然在4-7天时AChE/NGFr阳性细胞的萎缩和数量减少就已明显，但实际的细胞丢失（即FG预标记细胞的丢失）直到损伤后4周才明显。持续脑室内注射NGF（0.15微克/天）能够对抗所有三种类型的变化。注射2周可逆转萎缩以及AChE/NGFr染色的丢失，而注射4周则完全防止了后期发生的细胞丢失。此外，NGF注射可导致基底核和纹状体中未受损胆碱能神经元显著肥大。得出的结论是，在轴突切断的海马-隔区系统中，AChE和NGFr等标记蛋白的下调以及细胞萎缩先于细胞死亡，并且约1/3的轴突切断的隔区胆碱能神经元可能在下调的萎缩状态下长期存活。外源性NGF可预防萎缩和退行性变过程。
