title: Effects of prenatal stress and monoaminergic perturbations on the expression of serotonin 5-HT₄ and adrenergic β₂ receptors in the embryonic mouse telencephalon.
abstract: The serotonin 5-HT(4) receptor (5-HT(4)R) 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(4)Rs are important in forebrain function (including forebrain control of serotonergic activity in the brainstem), we investigated the susceptibility of 5-HT(4)R 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(2)AR) is embedded in the 5-HT(4)R gene, we also investigated whether 5-HT(4)R mRNA levels were modulated by selective β(2)AR 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(4)R splice variants and β(2)AR 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(2)AR agonist) and ICI 118,551 (a selective β(2)AR antagonist) had no effect on β(2)AR and 5-HT(4)R mRNA levels. These results show that prenatal stress and reduced 5-HT levels can alter 5-HT(4)R expression in the developing forebrain and that some 5-HT(4)R splice variants may be more susceptible than others.
authors.affiliation: Department of Psychological and Brain Sciences, University of California, Santa Barbara, CA 93106-9660, USA.
authors.forename: Angela
authors.initials: A
authors.lastname: Chen
authors.forename: Lauren D S
authors.initials: LD
authors.lastname: Kelley
authors.forename: Skirmantas
authors.initials: S
authors.lastname: Janušonis
mesh_terms: D058666:Adrenergic beta-2 Receptor Agonists / Q000494:pharmacology; D058672:Adrenergic beta-2 Receptor Antagonists / Q000494:pharmacology; D000704:Analysis of Variance; D000818:Animals; D004622:Embryo, Mammalian; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D010134:Fenclonine / Q000494:pharmacology; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000209:etiology / Q000473:pathology*; D011412:Propanolamines / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D011897:Random Allocation; D018343:Receptors, Adrenergic, beta-2 / Q000235:genetics / Q000378:metabolism*; D044422:Receptors, Serotonin, 5-HT4 / Q000235:genetics / Q000378:metabolism*; D013315:Stress, Psychological / Q000150:complications; D013687:Telencephalon / Q000196:embryology / Q000378:metabolism*; D013726:Terbutaline / Q000494:pharmacology
chemical_list: D058666:Adrenergic beta-2 Receptor Agonists; D058672:Adrenergic beta-2 Receptor Antagonists; D004791:Enzyme Inhibitors; D011412:Propanolamines; D012333:RNA, Messenger; D018343:Receptors, Adrenergic, beta-2; D044422:Receptors, Serotonin, 5-HT4; C026777:ICI 118551; D013726:Terbutaline; D010134:Fenclonine