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中脑多巴胺神经元对大脑中神经肽基因的表达有不同的调节作用。

Neuropeptide gene expression in brain is differentially regulated by midbrain dopamine neurons.

作者信息

Lindefors N, Brené S, Herrera-Marschitz M, Persson H

机构信息

Department of Medical Chemistry, Karolinska Institutet, Stockholm, Sweden.

出版信息

Exp Brain Res. 1990;80(3):489-500. doi: 10.1007/BF00227990.

DOI:10.1007/BF00227990
PMID:2387350
Abstract

In situ hybridization was used to study the expression of prepro-neuropeptide Y (NPY), preprosomatostatin (SOM), preprotachykinin (PPT) and preprocholecystokinin (CCK) mRNA in caudate-putamen and frontoparietal cortex of rat brain with unilateral lesion of midbrain dopamine neurons. Neurons expressing NPY and SOM mRNA showed a similar distribution and the expression of both NPY and SOM appears to be regulated by dopamine in a similar fashion. Following a dopamine deafferentation, the numerical density of both NPY and SOM mRNA producing neurons almost doubled in the lesioned caudate-putamen with no change in the average grain density over positive neurons. Hence, in the intact caudate-putamen dopamine appears to suppress expression of these two neuropeptide genes leading to an activation of both NPY and SOM mRNA expression in many non- or low-expressing neurons when the level of dopamine is decreased. In the fronto-parietal cortex, on the other hand, dopamine appears to stimulate NPY and SOM gene expression. Thus, in the absence of dopamine about half of the NPY positive neurons disappeared. However, for SOM the number of positive neurons did not change, but rather most positive neurons appeared to have down-regulated their SOM mRNA expression. No evidence was found for a change in CCK mRNA expression by the dopamine deafferentation, while PPT mRNA expression decreased in the deafferented caudate-putamen. Consequently, dopamine exerts dissimilar effects on the expression of different neuropeptide genes, that in turn do not respond in the same way in different brain regions.

摘要

采用原位杂交技术研究了中脑多巴胺神经元单侧损伤大鼠脑尾状核 - 壳核及额顶叶皮质中前神经肽Y(NPY)、前生长抑素(SOM)、前速激肽(PPT)和前胆囊收缩素(CCK)mRNA的表达。表达NPY和SOM mRNA的神经元分布相似,且NPY和SOM的表达似乎受多巴胺以相似方式调控。多巴胺去传入后,损伤的尾状核 - 壳核中产生NPY和SOM mRNA的神经元的数值密度几乎翻倍,而阳性神经元的平均颗粒密度无变化。因此,在完整的尾状核 - 壳核中,多巴胺似乎抑制这两种神经肽基因的表达,导致多巴胺水平降低时,许多非表达或低表达神经元中NPY和SOM mRNA表达激活。另一方面,在额顶叶皮质中,多巴胺似乎刺激NPY和SOM基因表达。因此,在缺乏多巴胺的情况下,约一半的NPY阳性神经元消失。然而,对于SOM,阳性神经元数量未变,而是大多数阳性神经元似乎下调了其SOM mRNA表达。未发现多巴胺去传入导致CCK mRNA表达改变的证据,而在去传入的尾状核 - 壳核中PPT mRNA表达降低。因此,多巴胺对不同神经肽基因的表达产生不同影响,而这些基因在不同脑区的反应方式也不相同。

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