Chronic glucocorticoid receptor activation impairs CREB transcriptional activity in clonal neurons
Excessive circulating levels of glucocorticoids are thought to be associated with cognitive impairment. We provide evidence that chronic activation of the glucocorticoid receptor (GR) in clonal neurons inhibits the transcriptional activity of the cyclic AMP response element-binding protein (CREB), w...
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| Veröffentlicht in: | Biochemical and biophysical research communications 2003-05, Vol.304 (4), p.720-723 |
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| container_title | Biochemical and biophysical research communications |
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| creator | Föcking, Melanie Hölker, Irmgard Trapp, Thorsten |
| description | Excessive circulating levels of glucocorticoids are thought to be associated with cognitive impairment. We provide evidence that chronic activation of the glucocorticoid receptor (GR) in clonal neurons inhibits the transcriptional activity of the cyclic AMP response element-binding protein (CREB), which is believed to be involved in memory processes. To investigate the underlying mechanism we studied the phosphorylation of CREB and found altered phosphorylation kinetics in neurons chronically treated with glucocorticoids. Our results demonstrate a hitherto unrecognized crosstalk between the cyclic AMP and glucocorticoid pathway and may provide the molecular basis for the effects of long-term glucocorticoid exposure on cognitive function. |
| doi_str_mv | 10.1016/S0006-291X(03)00665-X |
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We provide evidence that chronic activation of the glucocorticoid receptor (GR) in clonal neurons inhibits the transcriptional activity of the cyclic AMP response element-binding protein (CREB), which is believed to be involved in memory processes. To investigate the underlying mechanism we studied the phosphorylation of CREB and found altered phosphorylation kinetics in neurons chronically treated with glucocorticoids. Our results demonstrate a hitherto unrecognized crosstalk between the cyclic AMP and glucocorticoid pathway and may provide the molecular basis for the effects of long-term glucocorticoid exposure on cognitive function.</description><identifier>ISSN: 0006-291X</identifier><identifier>EISSN: 1090-2104</identifier><identifier>DOI: 10.1016/S0006-291X(03)00665-X</identifier><identifier>PMID: 12727214</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Animals ; cAMP ; Cell Line ; Colforsin - pharmacology ; CREB ; Cyclic AMP Response Element-Binding Protein - metabolism ; Dexamethasone ; Dexamethasone - pharmacology ; Genes, Reporter ; Glucocorticoid receptor ; Glucocorticoids - pharmacology ; Hippocampus - cytology ; Hippocampus - metabolism ; Memory ; Mice ; Neurons - drug effects ; Neurons - physiology ; Phosphorylation ; Receptors, Glucocorticoid - metabolism ; Signal Transduction - physiology ; Transcription, Genetic ; Transcriptional regulation</subject><ispartof>Biochemical and biophysical research communications, 2003-05, Vol.304 (4), p.720-723</ispartof><rights>2003 Elsevier Science (USA)</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c392t-e02aa3afb43a3ce8218b72ecbc9506e2a926e892935495f20e61086621d9cc7a3</citedby><cites>FETCH-LOGICAL-c392t-e02aa3afb43a3ce8218b72ecbc9506e2a926e892935495f20e61086621d9cc7a3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0006291X0300665X$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3537,27903,27904,65309</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/12727214$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Föcking, Melanie</creatorcontrib><creatorcontrib>Hölker, Irmgard</creatorcontrib><creatorcontrib>Trapp, Thorsten</creatorcontrib><title>Chronic glucocorticoid receptor activation impairs CREB transcriptional activity in clonal neurons</title><title>Biochemical and biophysical research communications</title><addtitle>Biochem Biophys Res Commun</addtitle><description>Excessive circulating levels of glucocorticoids are thought to be associated with cognitive impairment. We provide evidence that chronic activation of the glucocorticoid receptor (GR) in clonal neurons inhibits the transcriptional activity of the cyclic AMP response element-binding protein (CREB), which is believed to be involved in memory processes. To investigate the underlying mechanism we studied the phosphorylation of CREB and found altered phosphorylation kinetics in neurons chronically treated with glucocorticoids. Our results demonstrate a hitherto unrecognized crosstalk between the cyclic AMP and glucocorticoid pathway and may provide the molecular basis for the effects of long-term glucocorticoid exposure on cognitive function.</description><subject>Animals</subject><subject>cAMP</subject><subject>Cell Line</subject><subject>Colforsin - pharmacology</subject><subject>CREB</subject><subject>Cyclic AMP Response Element-Binding Protein - metabolism</subject><subject>Dexamethasone</subject><subject>Dexamethasone - pharmacology</subject><subject>Genes, Reporter</subject><subject>Glucocorticoid receptor</subject><subject>Glucocorticoids - pharmacology</subject><subject>Hippocampus - cytology</subject><subject>Hippocampus - metabolism</subject><subject>Memory</subject><subject>Mice</subject><subject>Neurons - drug effects</subject><subject>Neurons - physiology</subject><subject>Phosphorylation</subject><subject>Receptors, Glucocorticoid - metabolism</subject><subject>Signal Transduction - physiology</subject><subject>Transcription, Genetic</subject><subject>Transcriptional regulation</subject><issn>0006-291X</issn><issn>1090-2104</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2003</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkU1r3DAQhkVJaTZJf0KLT6E9OBlJtmydSrrkCwKFfMDehDyebVW8liPJgfz72rtLegxzmGHmmRl4X8a-cDjjwNX5AwCoXGi--gby-1SrMl99YAsOGnLBoThgizfkkB3F-BeA80LpT-yQi2oKXixYs_wTfO8w-92N6NGH5NC7NguENCQfMovJvdjkfJ-5zWBdiNny_vJnloLtIwY3zCPb7TiXXjPXZ9htWz2N0-14wj6ubRfp8z4fs6ery8flTX736_p2eXGXo9Qi5QTCWmnXTSGtRKoFr5tKEDaoS1AkrBaKai20LAtdrgWQ4lArJXirESsrj9np7u4Q_PNIMZmNi0hdZ3vyYzSVFLKSpX4X5HU1szNY7kAMPsZAazMEt7Hh1XAwswtm64KZJTYgzdYFs5r2vu4fjM2G2v9be9kn4McOoEmPF0fBRHTUI7VuEj6Z1rt3XvwDzv-ZAA</recordid><startdate>20030516</startdate><enddate>20030516</enddate><creator>Föcking, Melanie</creator><creator>Hölker, Irmgard</creator><creator>Trapp, Thorsten</creator><general>Elsevier Inc</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7TM</scope><scope>7X8</scope></search><sort><creationdate>20030516</creationdate><title>Chronic glucocorticoid receptor activation impairs CREB transcriptional activity in clonal neurons</title><author>Föcking, Melanie ; Hölker, Irmgard ; Trapp, Thorsten</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c392t-e02aa3afb43a3ce8218b72ecbc9506e2a926e892935495f20e61086621d9cc7a3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2003</creationdate><topic>Animals</topic><topic>cAMP</topic><topic>Cell Line</topic><topic>Colforsin - pharmacology</topic><topic>CREB</topic><topic>Cyclic AMP Response Element-Binding Protein - metabolism</topic><topic>Dexamethasone</topic><topic>Dexamethasone - pharmacology</topic><topic>Genes, Reporter</topic><topic>Glucocorticoid receptor</topic><topic>Glucocorticoids - pharmacology</topic><topic>Hippocampus - cytology</topic><topic>Hippocampus - metabolism</topic><topic>Memory</topic><topic>Mice</topic><topic>Neurons - drug effects</topic><topic>Neurons - physiology</topic><topic>Phosphorylation</topic><topic>Receptors, Glucocorticoid - metabolism</topic><topic>Signal Transduction - physiology</topic><topic>Transcription, Genetic</topic><topic>Transcriptional regulation</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Föcking, Melanie</creatorcontrib><creatorcontrib>Hölker, Irmgard</creatorcontrib><creatorcontrib>Trapp, Thorsten</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Nucleic Acids Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Biochemical and biophysical research communications</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Föcking, Melanie</au><au>Hölker, Irmgard</au><au>Trapp, Thorsten</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Chronic glucocorticoid receptor activation impairs CREB transcriptional activity in clonal neurons</atitle><jtitle>Biochemical and biophysical research communications</jtitle><addtitle>Biochem Biophys Res Commun</addtitle><date>2003-05-16</date><risdate>2003</risdate><volume>304</volume><issue>4</issue><spage>720</spage><epage>723</epage><pages>720-723</pages><issn>0006-291X</issn><eissn>1090-2104</eissn><abstract>Excessive circulating levels of glucocorticoids are thought to be associated with cognitive impairment. 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| ispartof | Biochemical and biophysical research communications, 2003-05, Vol.304 (4), p.720-723 |
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| source | MEDLINE; Elsevier ScienceDirect Journals |
| subjects | Animals cAMP Cell Line Colforsin - pharmacology CREB Cyclic AMP Response Element-Binding Protein - metabolism Dexamethasone Dexamethasone - pharmacology Genes, Reporter Glucocorticoid receptor Glucocorticoids - pharmacology Hippocampus - cytology Hippocampus - metabolism Memory Mice Neurons - drug effects Neurons - physiology Phosphorylation Receptors, Glucocorticoid - metabolism Signal Transduction - physiology Transcription, Genetic Transcriptional regulation |
| title | Chronic glucocorticoid receptor activation impairs CREB transcriptional activity in clonal neurons |
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