Catechol O-methyltransferase mRNA expression in human and rat brain:: Evidence for a role in cortical neuronal function
Catechol O-methyltransferase mRNA expression in human and rat brain:: Evidence for a role in cortical neuronal function
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DOI：
10.1016/s0306-4522(02)00556-0
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发表时间：
2003-01-01
期刊：
影响因子：
3.3
通讯作者：
Weinberger, DR
中科院分区：
文献类型：
--
作者：
Matsumoto, M;Weickert, CS;Weinberger, DR
儿茶酚O-甲基转移酶(COMT)参与儿茶酚胺的失活，包括神经递质多巴胺。COMT基因的Val(108/158)Met功能多态性已被证明影响人类与工作记忆相关的额叶功能。本研究采用原位杂交组织化学方法，研究了COMT在人前额叶皮质、纹状体、中脑及大鼠前脑中的表达。在两种动物中，在前额叶皮质各皮质层的大锥体和小神经元以及纹状体的中、大神经元均可观察到COMT mRNA信号。COMT基因在神经元中的表达水平明显高于胶质细胞。纹状体接受密集的多巴胺能输入，与前额叶皮质相比，COMT mRNA的表达水平较低。与以前的蛋白质表达数据一致，COMT mRNA在脑室内的室管膜细胞中含量丰富。在中脑，两个物种的多巴胺能神经元中都检测到了COMT mRNA，尽管水平很低。在大鼠前脑，脉络丛、海马齿状回和Ammon‘s角神经元也有密集标记。与COMT主要在非神经细胞表达的预期相反，本研究表明，神经元是在前额叶皮质和纹状体表达COMT mRNA的主要细胞群。结合已有的蛋白质定位数据，本研究结果表明，与多巴胺有高亲和力的COMT的膜结合异构体在人脑皮质的神经元树突中表达，这与其在多巴胺能神经传递中发挥重要作用的功能证据相一致。爱思唯尔科学有限公司代表IBRO出版。
Catechol O-methyltransferase (COMT) is involved in the inactivation of catecholamines, including the neurotransmitter dopamine. A Val(108/158) Met functional polymorphism of the COMT gene has been shown to affect working memory-associated frontal lobe function in humans. In the present study, in situ hybridization histochemistry was employed to determine the mRNA expression profile of COMT in the human prefrontal cortex, striatum and midbrain and in the rat forebrain. In both species, COMT mRNA signals were observed in large pyramidal and smaller neurons in all cortical layers of the prefrontal cortex as well as in medium and large neurons in the striatum. Levels of COMT mRNA were obviously higher in neurons than in glia. The striatum, which receives a dense dopaminergic input, expressed lower levels of COMT mRNA as compared with the prefrontal cortex. Consistent with previous protein expression data, COMT mRNA was abundant in ependymal cells lining the cerebral ventricles. In the midbrain, COMT mRNA was detected in dopaminergic neurons in both species, albeit at low levels. In the rat forebrain, dense labeling was also detected in choroid plexus and hippocampal dentate gyrus and Ammon's horn neurons. Contrary to expectations that COMT would be expressed predominantly in non-neuronal cells, the present study shows that neurons are the main cell populations expressing COMT mRNA in the prefrontal cortex and striatum. Combined with previous data about protein localization, the present results suggest that the membrane-bound isoform of COMT having a high affinity for dopamine is expressed at neuronal dendritic processes in human cortex, consistent with functional evidence that it plays an important role in dopaminergic neurotransmission. Published by Elsevier Science Ltd on behalf of IBRO.