Burgevin M C, Castel M N, Quarteronet D, Chevet T, Laduron P M
Research Center, Rhône-Poulenc Rorer, Vitry sur Seine, France.
Neuroscience. 1992 Aug;49(3):627-33. doi: 10.1016/0306-4522(92)90232-q.
In previous studies we have shown that labelled neurotensin injected into the rat striatum was found to be transported retrogradely in dopaminergic neurons through a process which was receptor and microtubule dependent. Now, we show, by in situ hybridization, the consequences of the striatal injection of neurotensin on the gene expression of tyrosine hydroxylase in the substantia nigra. Rats were injected with neurotensin or its fragments in the striatum of one side and with saline or the inactive fragment on the other. The number of nigral cells expressing tyrosine hydroxylase mRNA was found to increase by 40% after injection of neurotensin or its active fragment (neurotensin 8-13). In the same experimental conditions, the inactive fragment (neurotensin 1-8) was without effect. Time-course experiments revealed that the tyrosine hydroxylase mRNA was increased 4 h after neurotensin injection but not at 1 or 16 h. The fact that the increase of mRNA parallels the appearance of labelled neurotensin in the substantia nigra indicates that the changes in the gene expression of tyrosine hydroxylase might be the consequence of the retrograde axonal transport of neurotensin. These results represent the first evidence for the existence of a long-distance retrograde signalling process in which the neuropeptide and presumably its receptor may serve as information molecule between synapses and the cell body.
在先前的研究中，我们已经表明，注入大鼠纹状体的标记神经降压素可通过一种受体和微管依赖性过程在多巴胺能神经元中逆行运输。现在，我们通过原位杂交展示了纹状体注射神经降压素对黑质中酪氨酸羟化酶基因表达的影响。给大鼠一侧纹状体注射神经降压素或其片段，另一侧注射生理盐水或无活性片段。发现注射神经降压素或其活性片段（神经降压素8 - 13）后，表达酪氨酸羟化酶mRNA的黑质细胞数量增加了40%。在相同实验条件下，无活性片段（神经降压素1 - 8）没有作用。时间进程实验表明，神经降压素注射后4小时酪氨酸羟化酶mRNA增加，但1小时或16小时时没有增加。mRNA增加与黑质中标记神经降压素的出现平行这一事实表明，酪氨酸羟化酶基因表达的变化可能是神经降压素逆行轴突运输的结果。这些结果代表了长距离逆行信号传导过程存在的首个证据，其中神经肽及其受体可能作为突触和细胞体之间的信息分子。
