Limbic corticotropin-releasing hormone receptor 1 mediates anxiety-related behavior and hormonal adaptation to stress
Corticotropin-releasing hormone (CRH) is centrally involved in coordinating responses to a variety of stress-associated stimuli. Recent clinical data implicate CRH in the pathophysiology of human affective disorders. To differentiate the CNS pathways involving CRH and CRH receptor 1 (Crhr1) that mod...
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| Veröffentlicht in: | Nature neuroscience 2003-10, Vol.6 (10), p.1100-1107 |
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| creator | Müller, Marianne B Zimmermann, Stephan Sillaber, Inge Hagemeyer, Thomas P Deussing, Jan M Timpl, Peter Kormann, Michael S D Droste, Susanne K Kühn, Ralf Reul, Johannes M H M Holsboer, Florian Wurst, Wolfgang |
| description | Corticotropin-releasing hormone (CRH) is centrally involved in coordinating responses to a variety of stress-associated stimuli. Recent clinical data implicate CRH in the pathophysiology of human affective disorders. To differentiate the CNS pathways involving CRH and CRH receptor 1 (Crhr1) that modulate behavior from those that regulate neuroendocrine function, we generated a conditional knockout mouse line (
Crhr1
loxP/loxP
Camk2a-cre
) in which
Crhr1
function is inactivated postnatally in anterior forebrain and limbic brain structures, but not in the pituitary. This leaves the hypothalamic-pituitary-adrenocortical (HPA) system intact.
Crhr1
loxP/loxP
Camk2a-cre
mutants showed reduced anxiety, and the basal activity of their HPA system was normal. In contrast to
Crhr1
null mutants, conditional mutants were hypersensitive to stress corticotropin and corticosterone levels remained significantly elevated after stress. Our data clearly show that limbic
Crhr1
modulates anxiety-related behavior and that this effect is independent of HPA system function. Furthermore, we provide evidence for a new role of limbic
Crhr1
in neuroendocrine adaptation to stress. |
| doi_str_mv | 10.1038/nn1123 |
| format | Article |
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Crhr1
loxP/loxP
Camk2a-cre
) in which
Crhr1
function is inactivated postnatally in anterior forebrain and limbic brain structures, but not in the pituitary. This leaves the hypothalamic-pituitary-adrenocortical (HPA) system intact.
Crhr1
loxP/loxP
Camk2a-cre
mutants showed reduced anxiety, and the basal activity of their HPA system was normal. In contrast to
Crhr1
null mutants, conditional mutants were hypersensitive to stress corticotropin and corticosterone levels remained significantly elevated after stress. Our data clearly show that limbic
Crhr1
modulates anxiety-related behavior and that this effect is independent of HPA system function. Furthermore, we provide evidence for a new role of limbic
Crhr1
in neuroendocrine adaptation to stress.</description><identifier>ISSN: 1097-6256</identifier><identifier>EISSN: 1546-1726</identifier><identifier>DOI: 10.1038/nn1123</identifier><identifier>PMID: 12973355</identifier><identifier>CODEN: NANEFN</identifier><language>eng</language><publisher>New York: Nature Publishing Group US</publisher><subject>Adaptation, Physiological - genetics ; Animal Genetics and Genomics ; Animals ; Anxiety Disorders - genetics ; Anxiety Disorders - metabolism ; Anxiety Disorders - physiopathology ; Behavior, Animal - physiology ; Behavioral Sciences ; Biological Techniques ; Biomedical and Life Sciences ; Biomedicine ; Corticotropin-Releasing Hormone - metabolism ; Diagnosis ; Hormone receptors ; Human acts ; Human behavior ; Hypothalamo-Hypophyseal System - metabolism ; Hypothalamo-Hypophyseal System - physiopathology ; Limbic System - metabolism ; Limbic System - physiopathology ; Male ; Mice ; Mice, Knockout ; Mutation - genetics ; Neural Pathways - metabolism ; Neural Pathways - physiopathology ; Neurobiology ; Neurosciences ; Physiological aspects ; Pituitary-Adrenal System - metabolism ; Pituitary-Adrenal System - physiopathology ; Prosencephalon - metabolism ; Prosencephalon - physiopathology ; Psychological aspects ; Receptors, Corticotropin-Releasing Hormone - deficiency ; Receptors, Corticotropin-Releasing Hormone - genetics ; Receptors, Mineralocorticoid - genetics ; Risk factors ; RNA, Messenger - metabolism ; Stress (Psychology) ; Stress, Physiological - genetics ; Stress, Physiological - metabolism ; Stress, Physiological - physiopathology</subject><ispartof>Nature neuroscience, 2003-10, Vol.6 (10), p.1100-1107</ispartof><rights>Springer Nature America, Inc. 2003</rights><rights>COPYRIGHT 2003 Nature Publishing Group</rights><rights>Copyright Nature Publishing Group Oct 2003</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c504t-eef740c358d19aac8e9b314b7a6663bae10b23b9ffadf745b63dbe8756d5d03d3</citedby><cites>FETCH-LOGICAL-c504t-eef740c358d19aac8e9b314b7a6663bae10b23b9ffadf745b63dbe8756d5d03d3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1038/nn1123$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1038/nn1123$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,776,780,27901,27902,41464,42533,51294</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/12973355$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Müller, Marianne B</creatorcontrib><creatorcontrib>Zimmermann, Stephan</creatorcontrib><creatorcontrib>Sillaber, Inge</creatorcontrib><creatorcontrib>Hagemeyer, Thomas P</creatorcontrib><creatorcontrib>Deussing, Jan M</creatorcontrib><creatorcontrib>Timpl, Peter</creatorcontrib><creatorcontrib>Kormann, Michael S D</creatorcontrib><creatorcontrib>Droste, Susanne K</creatorcontrib><creatorcontrib>Kühn, Ralf</creatorcontrib><creatorcontrib>Reul, Johannes M H M</creatorcontrib><creatorcontrib>Holsboer, Florian</creatorcontrib><creatorcontrib>Wurst, Wolfgang</creatorcontrib><title>Limbic corticotropin-releasing hormone receptor 1 mediates anxiety-related behavior and hormonal adaptation to stress</title><title>Nature neuroscience</title><addtitle>Nat Neurosci</addtitle><addtitle>Nat Neurosci</addtitle><description>Corticotropin-releasing hormone (CRH) is centrally involved in coordinating responses to a variety of stress-associated stimuli. Recent clinical data implicate CRH in the pathophysiology of human affective disorders. To differentiate the CNS pathways involving CRH and CRH receptor 1 (Crhr1) that modulate behavior from those that regulate neuroendocrine function, we generated a conditional knockout mouse line (
Crhr1
loxP/loxP
Camk2a-cre
) in which
Crhr1
function is inactivated postnatally in anterior forebrain and limbic brain structures, but not in the pituitary. This leaves the hypothalamic-pituitary-adrenocortical (HPA) system intact.
Crhr1
loxP/loxP
Camk2a-cre
mutants showed reduced anxiety, and the basal activity of their HPA system was normal. In contrast to
Crhr1
null mutants, conditional mutants were hypersensitive to stress corticotropin and corticosterone levels remained significantly elevated after stress. Our data clearly show that limbic
Crhr1
modulates anxiety-related behavior and that this effect is independent of HPA system function. Furthermore, we provide evidence for a new role of limbic
Crhr1
in neuroendocrine adaptation to stress.</description><subject>Adaptation, Physiological - genetics</subject><subject>Animal Genetics and Genomics</subject><subject>Animals</subject><subject>Anxiety Disorders - genetics</subject><subject>Anxiety Disorders - metabolism</subject><subject>Anxiety Disorders - physiopathology</subject><subject>Behavior, Animal - physiology</subject><subject>Behavioral Sciences</subject><subject>Biological Techniques</subject><subject>Biomedical and Life Sciences</subject><subject>Biomedicine</subject><subject>Corticotropin-Releasing Hormone - metabolism</subject><subject>Diagnosis</subject><subject>Hormone receptors</subject><subject>Human acts</subject><subject>Human behavior</subject><subject>Hypothalamo-Hypophyseal System - metabolism</subject><subject>Hypothalamo-Hypophyseal System - physiopathology</subject><subject>Limbic System - metabolism</subject><subject>Limbic System - physiopathology</subject><subject>Male</subject><subject>Mice</subject><subject>Mice, Knockout</subject><subject>Mutation - genetics</subject><subject>Neural Pathways - metabolism</subject><subject>Neural Pathways - physiopathology</subject><subject>Neurobiology</subject><subject>Neurosciences</subject><subject>Physiological aspects</subject><subject>Pituitary-Adrenal System - metabolism</subject><subject>Pituitary-Adrenal System - physiopathology</subject><subject>Prosencephalon - metabolism</subject><subject>Prosencephalon - physiopathology</subject><subject>Psychological aspects</subject><subject>Receptors, Corticotropin-Releasing Hormone - deficiency</subject><subject>Receptors, Corticotropin-Releasing Hormone - genetics</subject><subject>Receptors, Mineralocorticoid - genetics</subject><subject>Risk factors</subject><subject>RNA, Messenger - metabolism</subject><subject>Stress (Psychology)</subject><subject>Stress, Physiological - genetics</subject><subject>Stress, Physiological - metabolism</subject><subject>Stress, Physiological - physiopathology</subject><issn>1097-6256</issn><issn>1546-1726</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2003</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNqFkstq3TAQhk1padK0fYQiumjpwqlkWRcvQ-glcKDQy9qMpfGJgi25khySt6-SYwjJpmgxkuabn7lV1VtGTxnl-rP3jDX8WXXMRCtrphr5vNxpp2rZCHlUvUrpilKqhO5eVkes6RTnQhxX687NgzPEhJidCTmGxfk64oSQnN-TyxDn4JFENLjkEAkjM1oHGRMBf-Mw397R5W3JgJdw7QoD3m6BMBGwsGTILniSA0k5YkqvqxcjTAnfbPak-vP1y-_z7_Xux7eL87NdbQRtc404qpYaLrRlHYDR2A2ctYMCKSUfABkdGj504wi2kGKQ3A6olZBWWMotP6k-HHSXGP6umHI_u2RwmsBjWFOvhGKq7Zr_gkxr3dFWFfD9E_AqrLHUmfqGU0k7fa92eoD2MGHv_Fj6CqYci3NpssfRlf8zpoUQur1X_fQooDAZb_Ie1pT6i18_H7NbqiaGlCKO_RLdDPG2Z7S_24X-sAsFfLelug5lZg_YNvwCfDwAqbj8HuNDLU-k_gGs6rzC</recordid><startdate>20031001</startdate><enddate>20031001</enddate><creator>Müller, Marianne B</creator><creator>Zimmermann, Stephan</creator><creator>Sillaber, Inge</creator><creator>Hagemeyer, Thomas P</creator><creator>Deussing, Jan M</creator><creator>Timpl, Peter</creator><creator>Kormann, Michael S D</creator><creator>Droste, Susanne K</creator><creator>Kühn, Ralf</creator><creator>Reul, Johannes M H M</creator><creator>Holsboer, Florian</creator><creator>Wurst, Wolfgang</creator><general>Nature Publishing Group US</general><general>Nature Publishing Group</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>ISR</scope><scope>3V.</scope><scope>7QG</scope><scope>7QP</scope><scope>7QR</scope><scope>7TK</scope><scope>7TM</scope><scope>7U7</scope><scope>7U9</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>88G</scope><scope>8AO</scope><scope>8FD</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M2M</scope><scope>M7P</scope><scope>P64</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>PSYQQ</scope><scope>Q9U</scope><scope>RC3</scope><scope>7X8</scope></search><sort><creationdate>20031001</creationdate><title>Limbic corticotropin-releasing hormone receptor 1 mediates anxiety-related behavior and hormonal adaptation to stress</title><author>Müller, Marianne B ; Zimmermann, Stephan ; Sillaber, Inge ; Hagemeyer, Thomas P ; Deussing, Jan M ; Timpl, Peter ; Kormann, Michael S D ; Droste, Susanne K ; Kühn, Ralf ; Reul, Johannes M H M ; Holsboer, Florian ; Wurst, Wolfgang</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c504t-eef740c358d19aac8e9b314b7a6663bae10b23b9ffadf745b63dbe8756d5d03d3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2003</creationdate><topic>Adaptation, Physiological - genetics</topic><topic>Animal Genetics and Genomics</topic><topic>Animals</topic><topic>Anxiety Disorders - genetics</topic><topic>Anxiety Disorders - metabolism</topic><topic>Anxiety Disorders - physiopathology</topic><topic>Behavior, Animal - physiology</topic><topic>Behavioral Sciences</topic><topic>Biological Techniques</topic><topic>Biomedical and Life Sciences</topic><topic>Biomedicine</topic><topic>Corticotropin-Releasing Hormone - metabolism</topic><topic>Diagnosis</topic><topic>Hormone receptors</topic><topic>Human acts</topic><topic>Human behavior</topic><topic>Hypothalamo-Hypophyseal System - metabolism</topic><topic>Hypothalamo-Hypophyseal System - physiopathology</topic><topic>Limbic System - metabolism</topic><topic>Limbic System - physiopathology</topic><topic>Male</topic><topic>Mice</topic><topic>Mice, Knockout</topic><topic>Mutation - genetics</topic><topic>Neural Pathways - metabolism</topic><topic>Neural Pathways - physiopathology</topic><topic>Neurobiology</topic><topic>Neurosciences</topic><topic>Physiological aspects</topic><topic>Pituitary-Adrenal System - metabolism</topic><topic>Pituitary-Adrenal System - physiopathology</topic><topic>Prosencephalon - metabolism</topic><topic>Prosencephalon - physiopathology</topic><topic>Psychological aspects</topic><topic>Receptors, Corticotropin-Releasing Hormone - deficiency</topic><topic>Receptors, Corticotropin-Releasing Hormone - genetics</topic><topic>Receptors, Mineralocorticoid - genetics</topic><topic>Risk factors</topic><topic>RNA, Messenger - metabolism</topic><topic>Stress (Psychology)</topic><topic>Stress, Physiological - genetics</topic><topic>Stress, Physiological - metabolism</topic><topic>Stress, Physiological - physiopathology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Müller, Marianne B</creatorcontrib><creatorcontrib>Zimmermann, Stephan</creatorcontrib><creatorcontrib>Sillaber, Inge</creatorcontrib><creatorcontrib>Hagemeyer, Thomas P</creatorcontrib><creatorcontrib>Deussing, Jan M</creatorcontrib><creatorcontrib>Timpl, Peter</creatorcontrib><creatorcontrib>Kormann, Michael S D</creatorcontrib><creatorcontrib>Droste, Susanne K</creatorcontrib><creatorcontrib>Kühn, Ralf</creatorcontrib><creatorcontrib>Reul, Johannes M H M</creatorcontrib><creatorcontrib>Holsboer, Florian</creatorcontrib><creatorcontrib>Wurst, Wolfgang</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Gale In Context: Science</collection><collection>ProQuest Central (Corporate)</collection><collection>Animal Behavior Abstracts</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Chemoreception Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Toxicology Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Psychology Database (Alumni)</collection><collection>ProQuest Pharma Collection</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>ProQuest Psychology</collection><collection>Biological Science Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>ProQuest One Psychology</collection><collection>ProQuest Central Basic</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Nature neuroscience</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Müller, Marianne B</au><au>Zimmermann, Stephan</au><au>Sillaber, Inge</au><au>Hagemeyer, Thomas P</au><au>Deussing, Jan M</au><au>Timpl, Peter</au><au>Kormann, Michael S D</au><au>Droste, Susanne K</au><au>Kühn, Ralf</au><au>Reul, Johannes M H M</au><au>Holsboer, Florian</au><au>Wurst, Wolfgang</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Limbic corticotropin-releasing hormone receptor 1 mediates anxiety-related behavior and hormonal adaptation to stress</atitle><jtitle>Nature neuroscience</jtitle><stitle>Nat Neurosci</stitle><addtitle>Nat Neurosci</addtitle><date>2003-10-01</date><risdate>2003</risdate><volume>6</volume><issue>10</issue><spage>1100</spage><epage>1107</epage><pages>1100-1107</pages><issn>1097-6256</issn><eissn>1546-1726</eissn><coden>NANEFN</coden><abstract>Corticotropin-releasing hormone (CRH) is centrally involved in coordinating responses to a variety of stress-associated stimuli. Recent clinical data implicate CRH in the pathophysiology of human affective disorders. To differentiate the CNS pathways involving CRH and CRH receptor 1 (Crhr1) that modulate behavior from those that regulate neuroendocrine function, we generated a conditional knockout mouse line (
Crhr1
loxP/loxP
Camk2a-cre
) in which
Crhr1
function is inactivated postnatally in anterior forebrain and limbic brain structures, but not in the pituitary. This leaves the hypothalamic-pituitary-adrenocortical (HPA) system intact.
Crhr1
loxP/loxP
Camk2a-cre
mutants showed reduced anxiety, and the basal activity of their HPA system was normal. In contrast to
Crhr1
null mutants, conditional mutants were hypersensitive to stress corticotropin and corticosterone levels remained significantly elevated after stress. Our data clearly show that limbic
Crhr1
modulates anxiety-related behavior and that this effect is independent of HPA system function. Furthermore, we provide evidence for a new role of limbic
Crhr1
in neuroendocrine adaptation to stress.</abstract><cop>New York</cop><pub>Nature Publishing Group US</pub><pmid>12973355</pmid><doi>10.1038/nn1123</doi><tpages>8</tpages></addata></record> |
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| ispartof | Nature neuroscience, 2003-10, Vol.6 (10), p.1100-1107 |
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| subjects | Adaptation, Physiological - genetics Animal Genetics and Genomics Animals Anxiety Disorders - genetics Anxiety Disorders - metabolism Anxiety Disorders - physiopathology Behavior, Animal - physiology Behavioral Sciences Biological Techniques Biomedical and Life Sciences Biomedicine Corticotropin-Releasing Hormone - metabolism Diagnosis Hormone receptors Human acts Human behavior Hypothalamo-Hypophyseal System - metabolism Hypothalamo-Hypophyseal System - physiopathology Limbic System - metabolism Limbic System - physiopathology Male Mice Mice, Knockout Mutation - genetics Neural Pathways - metabolism Neural Pathways - physiopathology Neurobiology Neurosciences Physiological aspects Pituitary-Adrenal System - metabolism Pituitary-Adrenal System - physiopathology Prosencephalon - metabolism Prosencephalon - physiopathology Psychological aspects Receptors, Corticotropin-Releasing Hormone - deficiency Receptors, Corticotropin-Releasing Hormone - genetics Receptors, Mineralocorticoid - genetics Risk factors RNA, Messenger - metabolism Stress (Psychology) Stress, Physiological - genetics Stress, Physiological - metabolism Stress, Physiological - physiopathology |
| title | Limbic corticotropin-releasing hormone receptor 1 mediates anxiety-related behavior and hormonal adaptation to stress |
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