Given the paucity of data on the distribution of serotonin (5-HT) receptors of type 6 (5-HT(6)) in the human brain, the aim of this study was to investigate their distribution in postmortem human prefrontal cortex, striatum and hippocampus by either immunohistochemical or immunofluorescence techniques. The brain samples were obtained from 6 subjects who had died for causes not involving primarily or secondarily the CNS. The 5-HT(6) receptor distribution was explored by the [(125)I]SB-258585 binding to brain membranes followed by immunohistochemical and immunofluorescence evaluations. A specific [(125)I]SB-258585 binding was detected in all the regions under investigation, whilst the content in the hippocampus and cortex being about 10-30 times lower than in the striatum. Immunohistochemistry and double-label immunofluorescence microscopy experiments, carried out in the prefrontal cortex and hippocampus only, since data in the striatum were already published, showed the presence of 5-HT(6) receptors in both pyramidal and glial cells of prefrontal cortex, while positive cells were mainly pyramidal neurons in the hippocampus. The heterogeneous distribution of 5-HT(6) receptors provides a preliminary explanation of how they might regulate different functions in different brain areas, such as, perhaps, brain trophism in the cortex and neuronal firing in the hippocampus. This study, taking into account all the limitations due to the postmortem model used, represents the starting point to explore the 5-HT(6) receptor functionality and its sub-cellular distribution.

译文

鉴于人脑中6型5-羟色胺 (5-HT(6)) 受体分布的数据很少,本研究的目的是通过免疫组织化学或免疫荧光技术研究其在死后人类前额叶皮层,纹状体和海马中的分布。大脑样本来自6名因不主要或次要涉及CNS的原因而死亡的受试者。5-羟色胺 (6) 受体分布通过 [(125)I]SB-258585与脑膜结合,然后进行免疫组织化学和免疫荧光评估来探索。在所研究的所有区域中检测到特定的 [(125)I]SB-258585结合,而海马和皮层的含量比纹状体低约10-30倍。免疫组织化学和双标记免疫荧光显微镜实验,仅在前额叶皮层和海马中进行,因为纹状体中的数据已经发表,显示在前额叶皮层的锥体和神经胶质细胞中都存在5-HT(6) 受体,而阳性细胞主要是海马中的锥体神经元。5-HT(6) 受体的异质分布提供了它们如何调节不同大脑区域的不同功能的初步解释,例如,也许,皮质中的脑营养和海马中的神经元放电。这项研究考虑到使用的死后模型所造成的所有局限性,代表了探索5-HT(6) 受体功能及其亚细胞分布的起点。

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