Paucity of enkephalin production in neostriatal striosomal neurons: analysis with preproenkephalin-green fluorescent protein transgenic mice
Paucity of enkephalin production in neostriatal striosomal neurons: analysis with preproenkephalin-green fluorescent protein transgenic mice
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DOI：
10.1111/j.1460-9568.2008.06502.x
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发表时间：
2008-11-01
影响因子：
3.4
通讯作者：
Kaneko, Takeshi
中科院分区：
文献类型：
--
作者：
Koshimizu, Yoshinori;Wu, Sheng-Xi;Kaneko, Takeshi
新纹状体的纹状体区室是否含有表达前脑啡肽原（PPE）的神经元仍然没有解决。为了通过开发灵敏的检测方法来解决这个问题，我们产生了在PPE基因的特异性转录控制下表达增强型绿色荧光蛋白（GFP）的转基因小鼠。建立了8个转基因株系，其中3个株系显示GFP表达，其分布与已报道的PPE mRNA在中枢神经系统中的定位一致。此外，在三个系的新纹状体的基质隔室中，强烈的GFP免疫反应密集地分布在神经元细胞体和神经元中，并且基质神经元显示> 94%的GFP和PPE免疫反应共定位。与此形成鲜明对比的是，GFP免疫反应性在纹状体区室中非常弱，其特征在于μ阿片受体（莫尔）的强烈免疫反应性。虽然新纹状体神经元分为GFP免疫阳性和阴性组的纹状体和基质室，GFP免疫反应的细胞体弱得多（类似1/5），在GFP阳性的纹状体神经元比在GFP阳性的基质神经元。PPE和莫尔表达的一个类似的相互组织也建议在腹侧纹状体，因为GFP的免疫反应是弱于强烈的MOR免疫阳性区域比周围的MOR阴性区域。由于PPE衍生肽是新纹状体中莫尔的内源性配体，并且基质神经元的轴突侧支很少进入纹状体区室，因此本研究结果提出了基质神经元大量产生的那些肽的靶点的问题。
Whether or not the striosome compartment of the neostriatum contained preproenkephalin (PPE)-expressing neurons remained unresolved. To address this question by developing a sensitive detection method, we generated transgenic mice expressing enhanced green fluorescent protein (GFP) under the specific transcriptional control of the PPE gene. Eight transgenic lines were established, and three of them showed GFP expression which was distributed in agreement with the reported localization of PPE mRNA in the central nervous system. Furthermore, in the matrix compartment of the neostriatum of the three lines, intense GFP immunoreactivity was densely distributed in the neuronal cell bodies and neuropil, and matrix neurons displayed > 94% co-localization for GFP and PPE immunoreactivities. In sharp contrast, GFP immunoreactivity was very weak in the striosome compartment, which was characterized by intense immunoreactivity for mu-opioid receptors (MOR). Although neostriatal neurons were divided into GFP-immunopositive and -negative groups in both the striosome and matrix compartments, GFP immunoreactivity of cell bodies was much weaker (similar to 1/5) in GFP-positive striosomal neurons than in GFP-positive matrix neurons. A similar reciprocal organization of PPE and MOR expression was also suggested in the ventral striatum, because GFP immunoreactivity was weaker in intensely MOR-immunopositive regions than in the surrounding MOR-negative regions. As PPE-derived peptides are endogenous ligands for MOR in the neostriatum and few axon collaterals of matrix neurons enter the striosome compartment, the present results raised the question of the target of those peptides produced abundantly by matrix neurons.