Effects of prenatal stress and monoaminergic perturbations on the expression of serotonin 5-HT₄ and adrenergic 尾₂ receptors in the embryonic mouse telencephalon

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• 作者：Angela Chen ; Lauren D.S. Kelley ; Skirmantas Janu&scaron ; onis ; ^{skirmantas.janusonis@psych.ucsb.edu}
• 关键词：Serotonin (5-hydroxytryptamine) ; 5-HT4 ; Norepinephrine ; Brain development ; Prenatal risk factors ; Nested genes
• 刊名：Brain Research
• 出版年：2012
• 期刊代码：8_00068993
• 类别：neu
• 出版时间：12 June, 2012
• 卷：1459
• 期：Complete
• 页码：27-34
• 文件大小：510 K

摘要

The serotonin 5-HT₄ receptor (5-HT₄R) is coded by a complex gene that produces four mRNA splice variants in mice (5-HT_4(a)R, 5-HT_4(b)R, 5-HT_4(e)R, 5-HT_4(f)R). This receptor has highly dynamic expression in brain development and its splice variants differ in their developmental trajectories. Since 5-HT₄Rs are important in forebrain function (including forebrain control of serotonergic activity in the brainstem), we investigated the susceptibility of 5-HT₄R expression in the mouse embryonic telencephalon to prenatal maternal stress and altered serotonin (5-hydroxytryptamine, 5-HT) levels. Because the gene coding the adrenergic 尾₂ receptor (尾₂AR) is embedded in the 5-HT₄R gene, we also investigated whether 5-HT₄R mRNA levels were modulated by selective 尾₂AR agents. Timed-pregnant C57BL/6 mice were treated beginning at embryonic day (E) 14 and quantitative reverse-transcription polymerase chain reaction (qRT-PCR) was used to assess the mRNA levels of all 5-HT₄R splice variants and 尾₂AR in the embryonic telencephalon at E17. Maternal prenatal stress and 5-HT depletion with pCPA, a tryptophan hydroxylase inhibitor, reduced the levels of the 5-HT_4(b)R splice variant. Terbutaline (a selective 尾₂AR agonist) and ICI 118,551 (a selective 尾₂AR antagonist) had no effect on 尾₂AR and 5-HT₄R mRNA levels. These results show that prenatal stress and reduced 5-HT levels can alter 5-HT₄R expression in the developing forebrain and that some 5-HT₄R splice variants may be more susceptible than others.