Sofroniew M V, Isacson O
Department of Anatomy, University of Cambridge, UK.
J Chem Neuroanat. 1988 Nov-Dec;1(6):327-37.
The degree of cell loss of immunohistochemically stained cholinergic neurons was quantitatively compared in equivalent regions of the septum in three groups of animals with lesions transecting their axons at different levels in the fimbria-fornix (FF). Locations of different septal regions and of FF lesions were defined according to their distances from fixed anatomical reference points. Individual animals all exhibited a gradient of cholinergic cell loss, such that the severity of cell loss diminished progressively in the rostral and ventral directions as the distance from the lesion increased beyond a certain point. Comparison of animals with FF lesions in different locations showed that this gradient of cell loss shifts in the caudo-rostral and dorso-ventral directions within the septal complex in direct relation to the proximity of the axotomizing FF lesion. These findings suggest that among septal cholinergic neurons there is a fixed spatial relationship between the distance of neuronal somata from an axotomizing FF lesion and the likelihood of neuronal loss in response to axotomy. This relationship could not be defined precisely using the material studied, but simple geometrical calculations showed that within 2500 microns of the lesion cell loss is always pronounced (less than 30 per cent detectable cells vs controls) and beyond 4000 microns cell loss is generally not severe (greater than 80 per cent detectable cells). Between these two distances cell loss diminishes in a gradiated manner. Thus, relatively small differences (1 mm) in the location of FF lesions can lead to marked differences in the severity of degeneration observed in certain equivalent regions of the septum. The findings have implications both for attempts to understand the causes underlying retrograde neuronal degeneration and for studies investigating means of preventing retrograde degeneration of cholinergic septal neurons.
在三组动物中，对经纤维束-穹窿（FF）不同水平轴突横断损伤的动物，在隔区的等效区域定量比较免疫组化染色的胆碱能神经元的细胞丢失程度。根据不同隔区和FF损伤部位与固定解剖参考点的距离来确定其位置。每只动物均呈现胆碱能细胞丢失梯度，即随着距损伤距离超过某一点后，细胞丢失的严重程度在 Rostral 和腹侧方向逐渐减轻。对不同部位有FF损伤的动物进行比较表明，隔复合体中这种细胞丢失梯度在尾-嘴侧和背-腹侧方向发生移位，与轴突切断性FF损伤的接近程度直接相关。这些发现表明，在隔区胆碱能神经元中，神经元胞体距轴突切断性FF损伤的距离与轴突切断后神经元丢失的可能性之间存在固定的空间关系。使用所研究的材料无法精确界定这种关系，但简单的几何计算表明，在距损伤2500微米范围内细胞丢失总是很明显（与对照组相比，可检测细胞少于30%），而在4000微米以外细胞丢失通常不严重（可检测细胞大于80%）。在这两个距离之间，细胞丢失以梯度方式减少。因此，FF损伤位置相对较小的差异（1毫米）可导致在隔区某些等效区域观察到的变性严重程度出现明显差异。这些发现对于理解逆行性神经元变性的潜在原因的尝试以及研究预防胆碱能隔区神经元逆行性变性方法的研究都具有重要意义。
