Increased expression of 5-HT_1B receptors by Herpes simplex virus gene transfer in septal neurons: New in vitro and in vivo models to study 5-HT_1B receptor function

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• 作者：Cé ; line Riegert ; Anna Katharina Rothmaier ; Jost Leemhuis ; Timothy J. Sexton ; John F. Neumaier ; Jean-Christophe Cassel ; Rolf Jackisch
• 关键词：Rat septal neurons ; Rat hippocampus ; CP-93 ; 129 ; Septal cell culture ; Herpes simplex virus
• 刊名：Brain Research Bulletin
• 出版年：2008
• 期刊代码：9_03619230
• 类别：neu
• 出版时间：1 July 2008
• 卷：76
• 期：4
• 页码：439-453
• 文件大小：3880 K

摘要

Serotonergic modulation of acetylcholine (ACh) release after neuron-specific increase of the expression of 5-HT_1B receptors by gene transfer was studied in vitro and in vivo. The increased expression of the 5-HT_1B receptor in vitro was induced by treating rat primary fetal septal cell cultures for 3 days with a viral vector inducing the expression of green fluorescent protein (GFP) vector alone, or, in addition, of 5-HT_1B receptors (HA1B/GFP vector). The transfection resulted in a high number of GFP-positive cells, part of which being immunopositive for choline acetyltransferase. In HA1B/GFP-cultures (vs. GFP-cultures), electrically evoked ACh release was significantly more sensitive to the inhibitory action of the 5-HT_1B agonist CP-93,129. Increased expression of the 5-HT_1B receptor in vivo was induced by stereotaxic injections of the vectors into the rat septal region. Three days later, electrically evoked release of ACh in hippocampal slices of HA1B/GFP-treated rats was lower than in their GFP-treated counterparts, showing a higher inhibitory efficacy of endogenous 5-HT on cholinergic terminals after transfection. Moreover, CP-93,129 had a higher inhibitory potency. In conclusion, the HA1B/GFP vector reveals a useful tool to induce a targeted increase of 5-HT_1B heteroreceptors on cholinergic neurons in selected CNS regions, which provides interesting perspectives for functional approaches at more integrated levels.