Effects of prenatal stress and monoaminergic perturbations on the expression of serotonin 5-HT 4 and adrenergic β 2 receptors in the embryonic mouse telencephalon

摘要

The serotonin 5-HT 4 receptor (5-HT 4R) 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-HT 4Rs are important in forebrain function (including forebrain control of serotonergic activity in the brainstem), we investigated the susceptibility of 5-HT 4R expression in the mouse embryonic telencephalon to prenatal maternal stress and altered serotonin (5-hydroxytryptamine, 5-HT) levels. Because the gene coding the adrenergic β 2 receptor (β 2AR) is embedded in the 5-HT 4R gene, we also investigated whether 5-HT 4R mRNA levels were modulated by selective β 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-HT 4R splice variants and β 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 β 2AR agonist) and ICI 118,551 (a selective β 2AR antagonist) had no effect on β 2AR and 5-HT 4R mRNA levels. These results show that prenatal stress and reduced 5-HT levels can alter 5-HT 4R expression in the developing forebrain and that some 5-HT 4R splice variants may be more susceptible than others.