Research ReportEffects of prenatal stress and monoaminergic perturbations on the expression of serotonin 5-HT4 and adrenergic β2 receptors in the embryonic mouse telencephalon

The serotonin 5-HT4 receptor (5-HT4R) is coded by a complex gene that produces four mRNA splice variants in mice (5-HT4(a)R, 5-HT4(b)R, 5-HT4(e)R, 5-HT4(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 β2 receptor (β2AR) is embedded in the 5-HT4R gene, we also investigated whether 5-HT4R mRNA levels were modulated by selective β2AR 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 β2AR 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-HT4(b)R splice variant. Terbutaline (a selective β2AR agonist) and ICI 118,551 (a selective β2AR antagonist) had no effect on β2AR 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.

► 5-HT4R is important for forebrain development and function. ► Prenatal stress and 5-HT depletion were studied in the developing mouse brain. ► Both conditions decreased 5-HT4(b)R mRNA levels in the embryonic telencephalon. ► No association was found between 5-HT4R and β2AR mRNA levels.