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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
1
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pubmed:dateCreated |
2009-6-15
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pubmed:abstractText |
Major depression is associated with both dysregulation of the hypothalamic pituitary adrenal axis and serotonergic deficiency, not the least of the 5-HT2A receptor. However, how these phenomena are linked to each other, and whether a low 5-HT2A receptor level is a state or a trait marker of depression is unknown. In mice with altered glucocorticoid receptor (GR) expression we investigated 5-HT2A receptor levels by Western blot and 3H-MDL100907 receptor binding. Serotonin fibre density was analyzed by stereological quantification of serotonin transporter immunopositive fibers. To establish an effect of GR activation on 5-HT2A levels, mature organotypic hippocampal cultures were exposed to corticosterone with or without GR antagonist mifepristone and mineralocorticoid receptor (MR) antagonist spironolactone. In GR under-expressing mice, hippocampal 5-HT2A receptor protein levels were decreased (26.3 +/- 1.6%, p < 0.05) and frontal 5-HT2A receptor binding was decreased (20 +/- 15%, p < 0.01) as compared to wild-type mice. Conversely, in over-expressing GR mice hippocampal 5-HT2A receptor protein levels were increased (60.8 +/- 4.0%, p = 0.0001) and 5-HT2A receptor binding was increased in dorsal hippocampus (77 +/- 35%, p < 0.05) as compared to wild-type mice. No difference in serotonin fibre density was observed in the GR over-expressing mice, while the GR under-expressing mice showed lower serotonergic innervation in the frontal cortex area. An effect of GR activation on 5-HT2A receptor levels was further corroborated by the culture studies as long-term exposure of 3 microM corticosterone to organotypic hippocampal cultures increased 5-HT2A receptor levels (p < 0.05). The corticosterone-induced 5-HT2A receptor up-regulation was blocked by addition of either spironolactone or mifepristone.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Aldosterone Antagonists,
http://linkedlifedata.com/resource/pubmed/chemical/Corticosterone,
http://linkedlifedata.com/resource/pubmed/chemical/Fluorobenzenes,
http://linkedlifedata.com/resource/pubmed/chemical/Hormone Antagonists,
http://linkedlifedata.com/resource/pubmed/chemical/MDL 100907,
http://linkedlifedata.com/resource/pubmed/chemical/Mifepristone,
http://linkedlifedata.com/resource/pubmed/chemical/Piperidines,
http://linkedlifedata.com/resource/pubmed/chemical/Receptor, Serotonin, 5-HT2A,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Glucocorticoid,
http://linkedlifedata.com/resource/pubmed/chemical/Serotonin Plasma Membrane...,
http://linkedlifedata.com/resource/pubmed/chemical/Spironolactone,
http://linkedlifedata.com/resource/pubmed/chemical/Tritium
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pubmed:status |
MEDLINE
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pubmed:month |
Jul
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pubmed:issn |
1090-2430
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pubmed:author |
pubmed-author:BrandweinChristianeC,
pubmed-author:Chorostowska-WynimkoJoannaJ,
pubmed-author:ChourbajiSabineS,
pubmed-author:GassPeterP,
pubmed-author:HalldinChristerC,
pubmed-author:KirkegaardLisbethL,
pubmed-author:KnudsenGitte MGM,
pubmed-author:KreyGesaG,
pubmed-author:MarcussenAnders BAB,
pubmed-author:RidderStephanieS,
pubmed-author:ThomsenMorten SMS,
pubmed-author:TrajkovskaViktorijaV
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pubmed:issnType |
Electronic
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pubmed:volume |
218
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
83-91
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pubmed:meshHeading |
pubmed-meshheading:19379741-Aldosterone Antagonists,
pubmed-meshheading:19379741-Analysis of Variance,
pubmed-meshheading:19379741-Animals,
pubmed-meshheading:19379741-Autoradiography,
pubmed-meshheading:19379741-Corticosterone,
pubmed-meshheading:19379741-Fluorobenzenes,
pubmed-meshheading:19379741-Gene Expression Regulation,
pubmed-meshheading:19379741-Hippocampus,
pubmed-meshheading:19379741-Hormone Antagonists,
pubmed-meshheading:19379741-Male,
pubmed-meshheading:19379741-Mice,
pubmed-meshheading:19379741-Mice, Inbred C57BL,
pubmed-meshheading:19379741-Mice, Transgenic,
pubmed-meshheading:19379741-Mifepristone,
pubmed-meshheading:19379741-Piperidines,
pubmed-meshheading:19379741-Protein Binding,
pubmed-meshheading:19379741-Rats,
pubmed-meshheading:19379741-Rats, Sprague-Dawley,
pubmed-meshheading:19379741-Receptor, Serotonin, 5-HT2A,
pubmed-meshheading:19379741-Receptors, Glucocorticoid,
pubmed-meshheading:19379741-Serotonin Plasma Membrane Transport Proteins,
pubmed-meshheading:19379741-Spironolactone,
pubmed-meshheading:19379741-Tissue Culture Techniques,
pubmed-meshheading:19379741-Tritium
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pubmed:year |
2009
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pubmed:articleTitle |
Activation of glucocorticoid receptors increases 5-HT2A receptor levels.
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pubmed:affiliation |
Neurobiology Research Unit and Centre for Integrated Molecular Brain Imaging (CIMBI), Copenhagen University Hospital, Unit 9201, Rigshospitalet, 9 Blegdamsvej, DK-2100 Copenhagen, Denmark.
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pubmed:publicationType |
Journal Article,
In Vitro,
Research Support, Non-U.S. Gov't
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