Luthman J, Eriksdotter-Nilsson M, Jonsson G
Department of Histology and Neurobiology, Karolinska Institut, Stockholm, Sweden.
Int J Dev Neurosci. 1990;8(1):107-18. doi: 10.1016/0736-5748(90)90027-y.
The effects of neonatal treatment with the antimitotic agent methylazoxymethanol and the catecholamine neurotoxin 6-hydroxydopamine on cerebellar morphology and monoamine innervation in the N.M.R.I. mouse has been studied. Methylazoxymethanol (25 mg/kg s.c.) treatment induced a cerebellar weight reduction of 40% as observed in the adult stage, while other CNS regions analysed were unaffected. An obvious atrophy of the cerebellar cortex was found, with an irregular distribution of the Purkinje cells, while Bergmann glia fibers deviated from their normal radial configuration and showed a tendency to form clusters. A 65% increase of tyrosine hydroxylase immunoreactive fiber density was found in the cerebellar cortex and 3H-5-hydroxytryptamine in vitro synaptosomal uptake was increased by 55%. Noradrenaline and 5-hydroxytryptamine concentrations in the cerebellum increased by 50 and 30%, respectively, whereas the total content of both neurotransmitters in cerebellum was approximately unchanged after methylazoxymethanol treatment. A significant reduction in total cerebellar in vitro binding of 3H-WB-4101 and 3H-dihydroalprenolol was also found, indicating compensatory receptor alterations following methylazoxymethanol treatment. The effect of combined treatment of methylazoxymethanol and the neurotoxin 6-hydroxydopamine (50 mg/kg s.c., day 1) showed a very pronounced reduction of noradrenaline concentration in cortex cerebri, while the noradrenaline concentration in cerebellum was increased by 185% and the tyrosine hydroxylase immunoreactive fiber density by 125%, indicating an additional relative hyperinnervation of cerebellar noradrenaline fiber due to a "pruning effect" of the 6-hydroxydopamine treatment. The results imply a relatively rigid development of terminal arborization of central nervous system monoamine neurons, relatively independent of neuronal and glial arrangement in the target area.
研究了抗有丝分裂剂甲基偶氮甲醇和儿茶酚胺神经毒素6-羟基多巴胺对N.M.R.I.小鼠小脑形态和单胺神经支配的新生期治疗效果。甲基偶氮甲醇（25mg/kg皮下注射）治疗导致成年期观察到的小脑重量减轻40%，而分析的其他中枢神经系统区域未受影响。发现小脑皮质明显萎缩，浦肯野细胞分布不规则，而伯格曼胶质纤维偏离其正常的放射状构型并显示出形成簇的趋势。在小脑皮质中发现酪氨酸羟化酶免疫反应性纤维密度增加65%，体外突触体对3H-5-羟色胺的摄取增加55%。小脑中去甲肾上腺素和5-羟色胺浓度分别增加50%和30%，而甲基偶氮甲醇治疗后小脑中两种神经递质的总含量大致不变。还发现3H-WB-4101和3H-二氢阿普洛尔的小脑体外总结合显著降低，表明甲基偶氮甲醇治疗后受体发生代偿性改变。甲基偶氮甲醇和神经毒素6-羟基多巴胺联合治疗（第1天50mg/kg皮下注射）的效果显示大脑皮质中去甲肾上腺素浓度非常明显降低，而小脑中去甲肾上腺素浓度增加185%，酪氨酸羟化酶免疫反应性纤维密度增加125%，表明由于6-羟基多巴胺治疗的“修剪效应”，小脑去甲肾上腺素纤维出现额外的相对超神经支配。结果表明中枢神经系统单胺神经元终末分支的发育相对固定，相对独立于靶区域中的神经元和胶质细胞排列。
