title: Rapid glucocorticoid effects on the expression of hippocampal neurotransmission-related genes.
abstract: We previously assessed corticosterone mediated gene expression in acute explant hippocampal slices and found over 200 responsive genes 1, 3 and 5 h after glucocorticoid receptor (GR) activation by a brief corticosterone pulse. Interestingly, 1 h after GR activation all genes were downregulated, many of which are involved in hippocampal neurotransmission and plasticity. The aim of the current experiment was 1) to measure the expression of several of these neurotransmission-related genes that were corticosterone-responsive 1 h after GR-activation in an in vivo setting, 2) to elucidate in which hippocampal subregion these expression changes take place and 3) to assess the specificity of regulation by activated GRs. For this purpose, rats were subcutaneously injected with vehicle, corticosterone or corticosterone pretreated with GR-antagonist RU38486. One hour after the corticosterone injections, mRNA expression levels of 5 selected genes were measured using in situ hybridization. The mineralocorticoid receptor (MR), MAO-A, casein kinase 2 and voltage dependent potassium mRNA's, but not dynein mRNA, were rapidly downregulated in vivo after corticosterone administration in hippocampal subregions. Furthermore, RU38486 pretreatment reversed in all cases these effects, illustrating the GR-specificity of transcriptional regulation by corticosterone. The results are important for understanding the role of GR in pleiotropic control of hippocampal neurotransmission and plasticity, which is characterized by recovery of function transiently raised by excitatory input.
authors: Division of Medical Pharmacology, Leiden/Amsterdam Center for Drug Research (LACDR), Leiden University Medical Center (LUMC), P.O. Box 9502, 2300 RA, Leiden, The Netherlands. maarten.morsink@gmail.com
authors: M C
authors: MC
authors: Morsink
authors: N G
authors: NG
authors: Van Gemert
authors: P J
authors: PJ
authors: Steenbergen
authors: M
authors: M
authors: Joëls
authors: E R
authors: ER
authors: De Kloet
authors: N A
authors: NA
authors: Datson
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D047390:Casein Kinase II / Q000235:genetics / Q000378:metabolism*; D004347:Drug Interactions; D005786:Gene Expression Regulation / Q000187:drug effects*; D005938:Glucocorticoids / Q000494:pharmacology*; D006624:Hippocampus / Q000187:drug effects*; D006727:Hormone Antagonists / Q000494:pharmacology; D017403:In Situ Hybridization / Q000379:methods; D008297:Male; D015735:Mifepristone / Q000494:pharmacology; D008995:Monoamine Oxidase / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D018161:Receptors, Mineralocorticoid / Q000235:genetics / Q000378:metabolism*; D051670:Shaw Potassium Channels / Q000235:genetics / Q000378:metabolism*
chemical_list: D005938:Glucocorticoids; D006727:Hormone Antagonists; D012333:RNA, Messenger; D018161:Receptors, Mineralocorticoid; D051670:Shaw Potassium Channels; D015735:Mifepristone; D008995:Monoamine Oxidase; D047390:Casein Kinase II