Noradrenaline synthesis by embryonic locus coeruleus neurons transplanted in adult rat brain - Influence of neuronal lesions inflicted on recipient animals -

从胚胎大鼠脑内制备含去甲肾上腺素能蓝斑(LC)神经元的神经细胞悬液，并将其移植到成年大鼠脑内。同时，移植神经元将其产物(S)提供给受体，其活动也受到受体状态的影响。据推测，损伤对神经元组织的损伤导致周围神经元组织中神经营养因子的增加。观察受体神经元组织对移植的去甲肾上腺素能神经元的影响。根据移植部位和损伤类型，设计两个系列的实验。在第一个系列中，胚胎神经元被移植到额叶皮质，受体动物在损毁前(损毁前组)或损毁后(LES…后)接受同侧LC电损伤多离子组)移植。损毁LC可使额叶皮质的内源性NA含量降至正常动物的20%左右。超过这个残留水平的NA含量被认为是由移植的神经元合成的。移植神经元合成NA的量在损伤前组和损伤后组几乎相同，提示移植部位预先去除内源性去甲肾上腺素能神经对移植神经元合成NA没有营养作用。在第二系列中，神经元移植到海马区，受体动物在移植前(前切断组)和后切断组(后切断组)接受同侧海马伞-穹隆切断。在这一系列实验中，动物在实验开始前3周切除同侧颈上神经节，以消除外周交感神经纤维在FF横断后进入海马区的情况。FF是各种传入和传出神经纤维进出海马区的通路，包括LC到海马区的去甲肾上腺素能纤维。坐骨神经切断后，大鼠海马区NA含量下降。对移植神经元合成的NA也进行了计算。损伤前组NA合成量高于损伤后组。整体实验结果表明，去甲肾上腺素能神经元的营养活动在受体动物体内的单一成分神经系统(LC去甲肾上腺素能投射)的消除并不能刺激移植的去甲肾上腺素能神经元的活动，但损伤可以延伸到传入和传出神经纤维的多个成分上。较少

Neuronal cell suspension containing noradrenergic locus coeruleus (LC) neurons was prepared from embryonic rat brain and was transplanted in adult rat brain. Meanwhile the transplanted neurons provide their product (s) to the recipient, their activities are also influenced by the condition of the recipient. It is supposed that lesions inflicted on the neuronal tissue result in the increase of neurotrophic factors in the surrounding neuronal tissue. Influences of recipient neuronal tissue exerted on the transplanted noradrenergic neurons were examined in either condition that the recipient had had any neuronal lesion or it had been intact when the neurons were transplanted.Two series of experiments were designed according to the site of the transplantation and the sort of the lesion. In the first series, the embryonic neurons were transplanted in the frontal cortex, and the recipient animals received ipsilateral electrical LC lesion before (the pre-lesioned group) or after (the post-les … More ioned group) the transplantation. The LC lesion reduced the intrinsic NA content in the frontal cortex to about 20% of that of the normal animals. The NA content beyond this residual level were thought to be synthesized by the transplanted neurons. The amount of NA synthesized by the transplanted neurons was almost equivalent in the pre-lesioned group and in the post-lesioned group, suggesting that the preceding removal of intrinsic noradrenergic innervation in the site of transplantation exerted no trophic effect on the synthesis of NA by the transplanted neurons.In the second series, the neurons were transplanted in the hippocampus, and the recipient animals received ipsilateral fimbria-fornix (FF) transection before (the pre-transected group) or after (the post-transected group) the transplantation. In this series, animals received the removal of the ipsilateral superior cervical ganglion 3 weeks prior to the beginning of the experiment in order to eliminate the ingrowth of peripheral sympathetic nerve fibers into the hippocampus following the FF transection. The FF is the rout of various afferent and efferent nerve fibers to and from the hippocampus, including the LC to hippocampal noradrenergic fibers. The NA content in the hippocampus decreased following the FF transection. The NA synthesized by the transplanted neurons was also calculated in this series. The amount of NA synthesized in the pre-transected group surpassed that in the post-lesioned group. The result indicated that the FF transection yielded the increase of trophic activity toward noradrenergic neurons in the hippocampus.We concluded from the overall experiments that the elimination of the mono-component nervous system (LC noradrenergic projection) in the recipient animal could not stimulate the activity of the transplanted noradrenergic neurons, but the lesion extended over several components of afferent and effrent nerve fibers could do so. Less