Developmental regulation of 5-HT1A receptor mRNA in the fetal limbic system: response to antenatal glucocorticoid.
The developmental changes in 5-HT1A receptor mRNA expression associated with advancing gestational age were examined in the fetal guinea pig hippocampus and dentate gyrus (DG) by in situ hybridization. We found that 5-HT1A receptor mRNA was present in the hippocampal CA1 subfield and dentate gyrus (DG), and was significantly (P < 0.05) elevated in the DG during the period of rapid brain growth [gestational day (gd) 50; term = 70 days]. Glucocorticoids have been shown to alter 5-HT1A receptor mRNA expression in the adult, but nothing is known about their impact on the developing fetal brain. Expression of 5-HT1A receptor mRNA in the fetal hippocampus was measured following repeated maternal administration (gd40, 41, 50, 51, 60 and 61) of synthetic glucocorticoid (dexamethasone; 1 and 10 mg/kg). Levels of 5-HT1A receptor mRNA were significantly (P < 0.005) elevated in CA1 and DG following repeated exposure to high-dose glucocorticoid (10 mg/kg) in male, but not in female fetuses. Because fetal exposure to glucocorticoids programs hypothalamo-pituitary-adrenal (HPA) function, and hippocampal serotonin is known to influence glucocorticoid receptor (GR) expression, the glucocorticoid-mediated changes in 5-HT1A receptor mRNA may play a role in the programming of HPA function.
Andrews
Marcus H
MH
Department of Physiology, Faculty of Medicine, University of Toronto, Medical Sciences Building, rm 3240, 1 King's College Circle, Toronto, Ontario, Canada M5S1A8. m.andrews@utoronto.ca
Kostaki
Alice
A
Setiawan
Elaine
E
McCabe
Lucy
L
Matthews
Stephen G
SG
D000704:Analysis of Variance; D000818:Animals; D001345:Autoradiography / Q000379:methods; D003907:Dexamethasone / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004622:Embryo, Mammalian; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects* / Q000502:physiology; D005938:Glucocorticoids / Q000494:pharmacology*; D006168:Guinea Pigs; D017403:In Situ Hybridization / Q000379:methods; D008032:Limbic System / Q000187:drug effects / Q000196:embryology / Q000378:metabolism*; D008297:Male; D011247:Pregnancy; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D044282:Receptor, Serotonin, 5-HT1A / Q000235:genetics / Q000378:metabolism*; D012737:Sex Factors
D005938:Glucocorticoids; D012333:RNA, Messenger; D044282:Receptor, Serotonin, 5-HT1A; D003907:Dexamethasone