Eriksdotter-Nilsson M, Skirboll S, Ebendal T, Olson L
Department of Histology and Neurobiology, Karolinska Institutet, Stockholm, Sweden.
Neuroscience. 1989;30(3):755-66. doi: 10.1016/0306-4522(89)90167-x.
The effects of nerve growth factor and antiserum against nerve growth factor on cortical cholinergic projection areas in the central nervous system and cerebellum were evaluated using intraocular grafts of cortex cerebri, hippocampus and cerebellum in rat hosts receiving injections into the anterior chamber of the eye of nerve growth factor (at transplantation, 5 and 10 days after transplantation) or antiserum to nerve growth factor (every 5 days). The controls received cytochrome c or preimmune serum. Growth of grafts was followed by repeated observations directly through the cornea of the host using a stereomicroscope. Nerve growth factor-treated grafts of cortex cerebri and hippocampus grew significantly smaller as compared to the corresponding control grafts. In one experiment, growth of cytochrome c and saline-treated cortex cerebri was compared and no difference in growth was found. Growth of nerve growth factor-treated cerebellar grafts did not differ significantly from growth of cytochrome c-treated grafts. Morphological analysis using Nissl-staining, antibodies to glial acidic fibrillary protein to evaluate the degree of gliosis and antiserum to neurofilament as a neuronal marker did not reveal any marked differences between nerve growth factor- and cytochrome c-treated grafts. Cortical grafts receiving anti-nerve growth factor antiserum by injection or by immunizing host rats against nerve growth factor showed similar growth to the controls. Similarly, grafts of fetal hippocampus to rats immunized with nerve growth factor were not significantly different from grafts to host rats immunized with cytochrome c. We conclude that exogenous nerve growth factor affects the development of grafted cortex cerebri and hippocampus. The fact that these cortical areas stop growing earlier in the presence of nerve growth factor without the grafts showing evidence of disturbed glial or neuronal populations compared to control grafts indicates that nerve growth factor acts to induce overall/premature differentiation and maturation. The mechanism for this whether or not it is receptor-mediated and which cells are primarily affected by nerve growth factor is not yet known.
利用大鼠宿主眼内移植大脑皮质、海马和小脑，通过向眼房内注射神经生长因子（移植时、移植后5天和10天）或抗神经生长因子抗血清（每5天一次），评估神经生长因子和抗神经生长因子抗血清对中枢神经系统和小脑中皮质胆碱能投射区域的影响。对照组接受细胞色素c或免疫前血清。使用体视显微镜通过宿主角膜直接反复观察移植物的生长情况。与相应的对照移植物相比，经神经生长因子处理的大脑皮质和海马移植物生长明显较小。在一项实验中，比较了细胞色素c和生理盐水处理的大脑皮质移植物的生长情况，未发现生长差异。经神经生长因子处理的小脑移植物的生长与经细胞色素c处理的移植物的生长无显著差异。使用尼氏染色、抗胶质酸性纤维蛋白抗体评估胶质增生程度以及抗神经丝抗血清作为神经元标志物进行形态学分析，未发现神经生长因子处理组和细胞色素c处理组移植物之间有任何明显差异。通过注射抗神经生长因子抗血清或使宿主大鼠对神经生长因子免疫的方式处理的皮质移植物，其生长情况与对照组相似。同样，将胎鼠海马移植到用神经生长因子免疫的大鼠体内，与移植到用细胞色素c免疫的宿主大鼠体内的移植物无显著差异。我们得出结论，外源性神经生长因子会影响移植的大脑皮质和海马的发育。在存在神经生长因子的情况下，这些皮质区域较早停止生长，与对照移植物相比，移植物未显示出胶质或神经元群体受干扰的迹象，这表明神经生长因子的作用是诱导整体/过早分化和成熟。其机制（是否由受体介导以及哪些细胞主要受神经生长因子影响）尚不清楚。
