Gage F H, Armstrong D M, Williams L R, Varon S
Department of Neurosciences, University of California, San Diego, School of Medicine, La Jolla 92093.
J Comp Neurol. 1988 Mar 1;269(1):147-55. doi: 10.1002/cne.902690112.
Septal efferent fibers from the neurons in the medial septal nucleus are destroyed by fimbria-fornix aspirative lesion. In the present study we used quantitative morphometric techniques to evaluate the response of these axotomized septal neurons to a constant infusion of nerve growth factor (NGF). By 2 weeks following the lesion, approximately 75% of the cholinergic neurons had degenerated in the untreated rats. The remaining cholinergic neurons showed few signs of the effect of the lesion when stained for a polyclonal antibody to ChAT and examined in 40-micron-thick sections. In 1-micron-thick sections the remaining ChAT-immunoreactive (IR) neurons also appeared no different from the intact ChAT neurons. However, non-ChAT-IR neurons had a shrunken nucleus, while all other morphometric parameters appeared normal. NGF infusion protected most of the ChAT-IR neurons from degenerating. The saved neurons had the same parameters as the undamaged ChAT-IR neurons when examined in either 40-micron- or 1-micron-thick sections. In addition, the shrunken appearance of the non-ChAT-IR neurons' nuclei was avoided by the NGF infusions. Enlarged ChAT-IR processes were evident in the dorsolateral quadrant of the septum following damage to the fimbria-fornix. NGF-infusions prevented the formation of these processes. Instead, in the treated animals the dorsal lateral quadrant contained a dense plexus of fine ChAT-IR varicosities. Taken together these results demonstrate that NGF not only can protect the cholinergic neurons from axotomy-induced degeneration but can also cause the saved neurons to maintain the same morphometric appearance as intact ChAT-IR neurons.(ABSTRACT TRUNCATED AT 250 WORDS)
来自内侧隔核神经元的隔传出纤维被穹窿海马伞抽吸性损伤破坏。在本研究中，我们使用定量形态测量技术来评估这些轴突切断的隔神经元对持续注入神经生长因子（NGF）的反应。损伤后2周，未治疗的大鼠中约75%的胆碱能神经元已退化。当用抗ChAT多克隆抗体染色并在40微米厚的切片中检查时，其余胆碱能神经元几乎没有损伤效应的迹象。在1微米厚的切片中，其余ChAT免疫反应性（IR）神经元与完整的ChAT神经元也没有差异。然而，非ChAT-IR神经元的细胞核缩小，而所有其他形态测量参数似乎正常。注入NGF可保护大多数ChAT-IR神经元不发生退化。在40微米或1微米厚的切片中检查时，保存下来的神经元与未受损的ChAT-IR神经元具有相同的参数。此外，注入NGF可避免非ChAT-IR神经元细胞核的缩小外观。穹窿海马伞损伤后，在隔区的背外侧象限可见ChAT-IR突起增大。注入NGF可阻止这些突起的形成。相反，在接受治疗的动物中，背外侧象限含有密集的细小ChAT-IR曲张丛。综上所述，这些结果表明，NGF不仅可以保护胆碱能神经元免受轴突切断诱导的退化，还可以使保存下来的神经元保持与完整ChAT-IR神经元相同的形态外观。（摘要截短至250字）
