Serotonin receptor of type 6 (5-HT6) in human prefrontal cortex and hippocampus post-mortem: An immunohistochemical and immunofluorescence study

Given the paucity of data on the distribution of serotonin (5-HT) receptors of type 6 (5-HT6) 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-HT6 receptor distribution was explored by the [125I]SB-258585 binding to brain membranes followed by immunohistochemical and immunofluorescence evaluations.A specific [125I]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-HT6 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-HT6 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-HT6 receptor functionality and its sub-cellular distribution.

► In prefrontal cortex, the immunoreactivity was present predominantly in the layer I.
► In the hippocampus, the immunoreactivity was present in the CA1-4 fields.
► The cells in the prefrontal cortex were co-localized with the glial marker.
► The cells in the hippocampus were co-localized with the neuronal marker.
► These findings suggest a sharp cellular regionality of 5-HT6 receptors.