The ERK phosphorylation levels in the amygdala predict anxiety symptoms in humans and MEK/ERK inhibition dissociates innate and learned defensive behaviors in rats
We demonstrate that the rate of extracellular signal-related kinase phosphorylation (P-ERK1,2/Total-ERK1,2) in the amygdala is negatively and independently associated with anxiety symptoms in 23 consecutive patients with drug-resistant mesial temporal lobe epilepsy that was surgically treated. In na...
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| Veröffentlicht in: | Molecular psychiatry 2021-12, Vol.26 (12), p.7257-7269 |
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| creator | de Carvalho, Cristiane Ribeiro Lopes, Mark William Constantino, Leandra C. Hoeller, Alexandre Ademar de Melo, Hiago Murilo Guarnieri, Ricardo Linhares, Marcelo Neves Bortolotto, Zuner Assis Prediger, Rui Daniel Latini, Alexandra Lin, Katia Licinio, Julio Leal, Rodrigo Bainy Walz, Roger |
| description | We demonstrate that the rate of extracellular signal-related kinase phosphorylation (P-ERK1,2/Total-ERK1,2) in the amygdala is negatively and independently associated with anxiety symptoms in 23 consecutive patients with drug-resistant mesial temporal lobe epilepsy that was surgically treated. In naive Wistar rats, the P-ERK1,2/Total-ERK1,2 ratio in the amygdala correlates negatively with innate anxiety-related behavior on the elevated plus maze (
n
= 20) but positively with expression of defensive-learned behavior (i.e., freezing) on Pavlovian aversive (fear) conditioning (
n
= 29). The microinfusion of ERK1/2 inhibitor (FR180204,
n
= 8–13/group) or MEK inhibitor (U0126,
n
= 8–9/group) into the basolateral amygdala did not affect anxiety-related behavior but impaired the evocation (anticipation) of conditioned-defensive behavior (
n
= 9–11/group). In conclusion, the P-ERK1,2/Total-ERK1,2 ratio in the amygdala predicts anxiety in humans and the innate anxiety- and conditioned freezing behaviors in rats. However, the ERK1/2 in the basolateral AMY is only required for the expression of defensive-learned behavior. These results support a dissociate ERK-dependent mechanism in the amygdala between innate anxiety-like responses and the anticipation of learned-defensive behavior. These findings have implications for understanding highly prevalent psychiatric disorders related to the defensive circuit manifested by anxiety and fear.
Highlights
The P-ERK1,2/Total-ERK1,2 ratio in the amygdala (AMY) correlates negatively with anxiety symptoms in patients with mesial temporal lobe epilepsy.
The P-ERK1,2/Total-ERK1,2 in the amygdala correlates negatively with the anxiety-like behavior and positively with freezing-learned behavior in naive rats.
ERK1,2 in the basolateral amygdala is required for learned-defensive but not for the anxiety-like behavior expression in rats. |
| doi_str_mv | 10.1038/s41380-021-01203-0 |
| format | Article |
| fullrecord | <record><control><sourceid>gale_proqu</sourceid><recordid>TN_cdi_proquest_miscellaneous_2555965557</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><galeid>A694903367</galeid><sourcerecordid>A694903367</sourcerecordid><originalsourceid>FETCH-LOGICAL-c552t-831a2af7ab94bffcb9ced88481260437f9efe3bb5455b0e5466408d8ee5136a93</originalsourceid><addsrcrecordid>eNp9kl9r1jAUxosobk6_gBcS8MabbkmTtOnlGK9_2ESQeR3S5vRtRpvUJH1ZP49f1LTvnCgiITkh53eecwJPlr0m-JxgKi4CI1TgHBckx6TANMdPslPCqjLnvBJP053yOmdEsJPsRQh3GK9J_jw7oYySEmN2mv247QHtvl6jqXchbb8MKhpn0QAHGAIyFsVEqHHZazUoNHnQpo1I2XsDcUFhGafoxg3s51HZkFIafd5dX6yqxvamMZugNiG41qgIK2xT3MgBlLegkYYObDAHQA306mCc3zS9iuFl9qxTQ4BXD_Es-_Z-d3v1Mb_58uHT1eVN3nJexFxQogrVVaqpWdN1bVO3oIVgghQlZrTq6tSCNg1nnDcYOCtLhoUWAJzQUtX0LHt31J28-z5DiHI0oYVhUBbcHGTBOa_LdFQJffsXeudmb9N0sihpwVLb1PKR2qsBpLGdi161q6i8LGtWY0rLVev8H1RaGkbTOgudSe9_FBTHgta7EDx0cvJmVH6RBMvVGfLoDJmcITdnSJyK3jxMPDcj6MeSX1ZIAD0CIaXsHvzvL_1H9ie-ecRb</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2632488404</pqid></control><display><type>article</type><title>The ERK phosphorylation levels in the amygdala predict anxiety symptoms in humans and MEK/ERK inhibition dissociates innate and learned defensive behaviors in rats</title><source>MEDLINE</source><source>Springer Nature - Complete Springer Journals</source><creator>de Carvalho, Cristiane Ribeiro ; Lopes, Mark William ; Constantino, Leandra C. ; Hoeller, Alexandre Ademar ; de Melo, Hiago Murilo ; Guarnieri, Ricardo ; Linhares, Marcelo Neves ; Bortolotto, Zuner Assis ; Prediger, Rui Daniel ; Latini, Alexandra ; Lin, Katia ; Licinio, Julio ; Leal, Rodrigo Bainy ; Walz, Roger</creator><creatorcontrib>de Carvalho, Cristiane Ribeiro ; Lopes, Mark William ; Constantino, Leandra C. ; Hoeller, Alexandre Ademar ; de Melo, Hiago Murilo ; Guarnieri, Ricardo ; Linhares, Marcelo Neves ; Bortolotto, Zuner Assis ; Prediger, Rui Daniel ; Latini, Alexandra ; Lin, Katia ; Licinio, Julio ; Leal, Rodrigo Bainy ; Walz, Roger</creatorcontrib><description>We demonstrate that the rate of extracellular signal-related kinase phosphorylation (P-ERK1,2/Total-ERK1,2) in the amygdala is negatively and independently associated with anxiety symptoms in 23 consecutive patients with drug-resistant mesial temporal lobe epilepsy that was surgically treated. In naive Wistar rats, the P-ERK1,2/Total-ERK1,2 ratio in the amygdala correlates negatively with innate anxiety-related behavior on the elevated plus maze (
n
= 20) but positively with expression of defensive-learned behavior (i.e., freezing) on Pavlovian aversive (fear) conditioning (
n
= 29). The microinfusion of ERK1/2 inhibitor (FR180204,
n
= 8–13/group) or MEK inhibitor (U0126,
n
= 8–9/group) into the basolateral amygdala did not affect anxiety-related behavior but impaired the evocation (anticipation) of conditioned-defensive behavior (
n
= 9–11/group). In conclusion, the P-ERK1,2/Total-ERK1,2 ratio in the amygdala predicts anxiety in humans and the innate anxiety- and conditioned freezing behaviors in rats. However, the ERK1/2 in the basolateral AMY is only required for the expression of defensive-learned behavior. These results support a dissociate ERK-dependent mechanism in the amygdala between innate anxiety-like responses and the anticipation of learned-defensive behavior. These findings have implications for understanding highly prevalent psychiatric disorders related to the defensive circuit manifested by anxiety and fear.
Highlights
The P-ERK1,2/Total-ERK1,2 ratio in the amygdala (AMY) correlates negatively with anxiety symptoms in patients with mesial temporal lobe epilepsy.
The P-ERK1,2/Total-ERK1,2 in the amygdala correlates negatively with the anxiety-like behavior and positively with freezing-learned behavior in naive rats.
ERK1,2 in the basolateral amygdala is required for learned-defensive but not for the anxiety-like behavior expression in rats.</description><identifier>ISSN: 1359-4184</identifier><identifier>EISSN: 1476-5578</identifier><identifier>DOI: 10.1038/s41380-021-01203-0</identifier><identifier>PMID: 34316004</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>631/337 ; 631/378 ; 631/45 ; 692/699/476 ; 82/80 ; Amygdala ; Amygdala (Brain) ; Amygdala - metabolism ; Animals ; Anxiety ; Anxiety - metabolism ; Behavior ; Behavioral Sciences ; Biological Psychology ; Complications and side effects ; Defensive behavior ; Defensiveness (Psychology) ; Development and progression ; Drug resistance ; Epilepsy ; Extracellular signal-regulated kinase ; Fear ; Health aspects ; Humans ; Learning ; Medicine ; Medicine & Public Health ; MEK inhibitors ; Mental disorders ; Mitogen-Activated Protein Kinase 1 - antagonists & inhibitors ; Mitogen-Activated Protein Kinase 1 - metabolism ; Mitogen-Activated Protein Kinase 3 - antagonists & inhibitors ; Mitogen-Activated Protein Kinase 3 - metabolism ; Mitogen-Activated Protein Kinase Kinases - metabolism ; Neurosciences ; Pharmacotherapy ; Phosphorylation ; Physiological aspects ; Protein kinases ; Psychiatric research ; Psychiatry ; Rats ; Rats, Wistar ; Risk factors ; Rodents ; Temporal lobe ; Temporal lobe epilepsy ; Tonic immobility</subject><ispartof>Molecular psychiatry, 2021-12, Vol.26 (12), p.7257-7269</ispartof><rights>The Author(s), under exclusive licence to Springer Nature Limited 2021</rights><rights>2021. The Author(s), under exclusive licence to Springer Nature Limited.</rights><rights>COPYRIGHT 2021 Nature Publishing Group</rights><rights>The Author(s), under exclusive licence to Springer Nature Limited 2021.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c552t-831a2af7ab94bffcb9ced88481260437f9efe3bb5455b0e5466408d8ee5136a93</citedby><cites>FETCH-LOGICAL-c552t-831a2af7ab94bffcb9ced88481260437f9efe3bb5455b0e5466408d8ee5136a93</cites><orcidid>0000-0001-7526-1502 ; 0000-0002-5401-7524 ; 0000-0002-5513-8061 ; 0000-0002-4435-6768 ; 0000-0003-0523-4351 ; 0000-0003-2536-6888 ; 0000-0002-5292-8455 ; 0000-0002-9875-6687 ; 0000-0002-8152-7773 ; 0000-0002-7547-6463 ; 0000-0001-6905-5884</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1038/s41380-021-01203-0$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1038/s41380-021-01203-0$$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/34316004$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>de Carvalho, Cristiane Ribeiro</creatorcontrib><creatorcontrib>Lopes, Mark William</creatorcontrib><creatorcontrib>Constantino, Leandra C.</creatorcontrib><creatorcontrib>Hoeller, Alexandre Ademar</creatorcontrib><creatorcontrib>de Melo, Hiago Murilo</creatorcontrib><creatorcontrib>Guarnieri, Ricardo</creatorcontrib><creatorcontrib>Linhares, Marcelo Neves</creatorcontrib><creatorcontrib>Bortolotto, Zuner Assis</creatorcontrib><creatorcontrib>Prediger, Rui Daniel</creatorcontrib><creatorcontrib>Latini, Alexandra</creatorcontrib><creatorcontrib>Lin, Katia</creatorcontrib><creatorcontrib>Licinio, Julio</creatorcontrib><creatorcontrib>Leal, Rodrigo Bainy</creatorcontrib><creatorcontrib>Walz, Roger</creatorcontrib><title>The ERK phosphorylation levels in the amygdala predict anxiety symptoms in humans and MEK/ERK inhibition dissociates innate and learned defensive behaviors in rats</title><title>Molecular psychiatry</title><addtitle>Mol Psychiatry</addtitle><addtitle>Mol Psychiatry</addtitle><description>We demonstrate that the rate of extracellular signal-related kinase phosphorylation (P-ERK1,2/Total-ERK1,2) in the amygdala is negatively and independently associated with anxiety symptoms in 23 consecutive patients with drug-resistant mesial temporal lobe epilepsy that was surgically treated. In naive Wistar rats, the P-ERK1,2/Total-ERK1,2 ratio in the amygdala correlates negatively with innate anxiety-related behavior on the elevated plus maze (
n
= 20) but positively with expression of defensive-learned behavior (i.e., freezing) on Pavlovian aversive (fear) conditioning (
n
= 29). The microinfusion of ERK1/2 inhibitor (FR180204,
n
= 8–13/group) or MEK inhibitor (U0126,
n
= 8–9/group) into the basolateral amygdala did not affect anxiety-related behavior but impaired the evocation (anticipation) of conditioned-defensive behavior (
n
= 9–11/group). In conclusion, the P-ERK1,2/Total-ERK1,2 ratio in the amygdala predicts anxiety in humans and the innate anxiety- and conditioned freezing behaviors in rats. However, the ERK1/2 in the basolateral AMY is only required for the expression of defensive-learned behavior. These results support a dissociate ERK-dependent mechanism in the amygdala between innate anxiety-like responses and the anticipation of learned-defensive behavior. These findings have implications for understanding highly prevalent psychiatric disorders related to the defensive circuit manifested by anxiety and fear.
Highlights
The P-ERK1,2/Total-ERK1,2 ratio in the amygdala (AMY) correlates negatively with anxiety symptoms in patients with mesial temporal lobe epilepsy.
The P-ERK1,2/Total-ERK1,2 in the amygdala correlates negatively with the anxiety-like behavior and positively with freezing-learned behavior in naive rats.
ERK1,2 in the basolateral amygdala is required for learned-defensive but not for the anxiety-like behavior expression in rats.</description><subject>631/337</subject><subject>631/378</subject><subject>631/45</subject><subject>692/699/476</subject><subject>82/80</subject><subject>Amygdala</subject><subject>Amygdala (Brain)</subject><subject>Amygdala - metabolism</subject><subject>Animals</subject><subject>Anxiety</subject><subject>Anxiety - metabolism</subject><subject>Behavior</subject><subject>Behavioral Sciences</subject><subject>Biological Psychology</subject><subject>Complications and side effects</subject><subject>Defensive behavior</subject><subject>Defensiveness (Psychology)</subject><subject>Development and progression</subject><subject>Drug resistance</subject><subject>Epilepsy</subject><subject>Extracellular signal-regulated kinase</subject><subject>Fear</subject><subject>Health aspects</subject><subject>Humans</subject><subject>Learning</subject><subject>Medicine</subject><subject>Medicine & Public Health</subject><subject>MEK inhibitors</subject><subject>Mental disorders</subject><subject>Mitogen-Activated Protein Kinase 1 - antagonists & inhibitors</subject><subject>Mitogen-Activated Protein Kinase 1 - metabolism</subject><subject>Mitogen-Activated Protein Kinase 3 - antagonists & inhibitors</subject><subject>Mitogen-Activated Protein Kinase 3 - metabolism</subject><subject>Mitogen-Activated Protein Kinase Kinases - metabolism</subject><subject>Neurosciences</subject><subject>Pharmacotherapy</subject><subject>Phosphorylation</subject><subject>Physiological aspects</subject><subject>Protein kinases</subject><subject>Psychiatric research</subject><subject>Psychiatry</subject><subject>Rats</subject><subject>Rats, Wistar</subject><subject>Risk factors</subject><subject>Rodents</subject><subject>Temporal lobe</subject><subject>Temporal lobe epilepsy</subject><subject>Tonic immobility</subject><issn>1359-4184</issn><issn>1476-5578</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNp9kl9r1jAUxosobk6_gBcS8MabbkmTtOnlGK9_2ESQeR3S5vRtRpvUJH1ZP49f1LTvnCgiITkh53eecwJPlr0m-JxgKi4CI1TgHBckx6TANMdPslPCqjLnvBJP053yOmdEsJPsRQh3GK9J_jw7oYySEmN2mv247QHtvl6jqXchbb8MKhpn0QAHGAIyFsVEqHHZazUoNHnQpo1I2XsDcUFhGafoxg3s51HZkFIafd5dX6yqxvamMZugNiG41qgIK2xT3MgBlLegkYYObDAHQA306mCc3zS9iuFl9qxTQ4BXD_Es-_Z-d3v1Mb_58uHT1eVN3nJexFxQogrVVaqpWdN1bVO3oIVgghQlZrTq6tSCNg1nnDcYOCtLhoUWAJzQUtX0LHt31J28-z5DiHI0oYVhUBbcHGTBOa_LdFQJffsXeudmb9N0sihpwVLb1PKR2qsBpLGdi161q6i8LGtWY0rLVev8H1RaGkbTOgudSe9_FBTHgta7EDx0cvJmVH6RBMvVGfLoDJmcITdnSJyK3jxMPDcj6MeSX1ZIAD0CIaXsHvzvL_1H9ie-ecRb</recordid><startdate>20211201</startdate><enddate>20211201</enddate><creator>de Carvalho, Cristiane Ribeiro</creator><creator>Lopes, Mark William</creator><creator>Constantino, Leandra C.</creator><creator>Hoeller, Alexandre Ademar</creator><creator>de Melo, Hiago Murilo</creator><creator>Guarnieri, Ricardo</creator><creator>Linhares, Marcelo Neves</creator><creator>Bortolotto, Zuner Assis</creator><creator>Prediger, Rui Daniel</creator><creator>Latini, Alexandra</creator><creator>Lin, Katia</creator><creator>Licinio, Julio</creator><creator>Leal, Rodrigo Bainy</creator><creator>Walz, Roger</creator><general>Nature Publishing Group UK</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>3V.</scope><scope>7TK</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>88G</scope><scope>8AO</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>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M2M</scope><scope>M7P</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>PSYQQ</scope><scope>Q9U</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0001-7526-1502</orcidid><orcidid>https://orcid.org/0000-0002-5401-7524</orcidid><orcidid>https://orcid.org/0000-0002-5513-8061</orcidid><orcidid>https://orcid.org/0000-0002-4435-6768</orcidid><orcidid>https://orcid.org/0000-0003-0523-4351</orcidid><orcidid>https://orcid.org/0000-0003-2536-6888</orcidid><orcidid>https://orcid.org/0000-0002-5292-8455</orcidid><orcidid>https://orcid.org/0000-0002-9875-6687</orcidid><orcidid>https://orcid.org/0000-0002-8152-7773</orcidid><orcidid>https://orcid.org/0000-0002-7547-6463</orcidid><orcidid>https://orcid.org/0000-0001-6905-5884</orcidid></search><sort><creationdate>20211201</creationdate><title>The ERK phosphorylation levels in the amygdala predict anxiety symptoms in humans and MEK/ERK inhibition dissociates innate and learned defensive behaviors in rats</title><author>de Carvalho, Cristiane Ribeiro ; Lopes, Mark William ; Constantino, Leandra C. ; Hoeller, Alexandre Ademar ; de Melo, Hiago Murilo ; Guarnieri, Ricardo ; Linhares, Marcelo Neves ; Bortolotto, Zuner Assis ; Prediger, Rui Daniel ; Latini, Alexandra ; Lin, Katia ; Licinio, Julio ; Leal, Rodrigo Bainy ; Walz, Roger</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c552t-831a2af7ab94bffcb9ced88481260437f9efe3bb5455b0e5466408d8ee5136a93</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>631/337</topic><topic>631/378</topic><topic>631/45</topic><topic>692/699/476</topic><topic>82/80</topic><topic>Amygdala</topic><topic>Amygdala (Brain)</topic><topic>Amygdala - metabolism</topic><topic>Animals</topic><topic>Anxiety</topic><topic>Anxiety - metabolism</topic><topic>Behavior</topic><topic>Behavioral Sciences</topic><topic>Biological Psychology</topic><topic>Complications and side effects</topic><topic>Defensive behavior</topic><topic>Defensiveness (Psychology)</topic><topic>Development and progression</topic><topic>Drug resistance</topic><topic>Epilepsy</topic><topic>Extracellular signal-regulated kinase</topic><topic>Fear</topic><topic>Health aspects</topic><topic>Humans</topic><topic>Learning</topic><topic>Medicine</topic><topic>Medicine & Public Health</topic><topic>MEK inhibitors</topic><topic>Mental disorders</topic><topic>Mitogen-Activated Protein Kinase 1 - antagonists & inhibitors</topic><topic>Mitogen-Activated Protein Kinase 1 - metabolism</topic><topic>Mitogen-Activated Protein Kinase 3 - antagonists & inhibitors</topic><topic>Mitogen-Activated Protein Kinase 3 - metabolism</topic><topic>Mitogen-Activated Protein Kinase Kinases - metabolism</topic><topic>Neurosciences</topic><topic>Pharmacotherapy</topic><topic>Phosphorylation</topic><topic>Physiological aspects</topic><topic>Protein kinases</topic><topic>Psychiatric research</topic><topic>Psychiatry</topic><topic>Rats</topic><topic>Rats, Wistar</topic><topic>Risk factors</topic><topic>Rodents</topic><topic>Temporal lobe</topic><topic>Temporal lobe epilepsy</topic><topic>Tonic immobility</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>de Carvalho, Cristiane Ribeiro</creatorcontrib><creatorcontrib>Lopes, Mark William</creatorcontrib><creatorcontrib>Constantino, Leandra C.</creatorcontrib><creatorcontrib>Hoeller, Alexandre Ademar</creatorcontrib><creatorcontrib>de Melo, Hiago Murilo</creatorcontrib><creatorcontrib>Guarnieri, Ricardo</creatorcontrib><creatorcontrib>Linhares, Marcelo Neves</creatorcontrib><creatorcontrib>Bortolotto, Zuner Assis</creatorcontrib><creatorcontrib>Prediger, Rui Daniel</creatorcontrib><creatorcontrib>Latini, Alexandra</creatorcontrib><creatorcontrib>Lin, Katia</creatorcontrib><creatorcontrib>Licinio, Julio</creatorcontrib><creatorcontrib>Leal, Rodrigo Bainy</creatorcontrib><creatorcontrib>Walz, Roger</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Neurosciences 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>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>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</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>Psychology Database</collection><collection>Biological Science Database</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>MEDLINE - Academic</collection><jtitle>Molecular psychiatry</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>de Carvalho, Cristiane Ribeiro</au><au>Lopes, Mark William</au><au>Constantino, Leandra C.</au><au>Hoeller, Alexandre Ademar</au><au>de Melo, Hiago Murilo</au><au>Guarnieri, Ricardo</au><au>Linhares, Marcelo Neves</au><au>Bortolotto, Zuner Assis</au><au>Prediger, Rui Daniel</au><au>Latini, Alexandra</au><au>Lin, Katia</au><au>Licinio, Julio</au><au>Leal, Rodrigo Bainy</au><au>Walz, Roger</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The ERK phosphorylation levels in the amygdala predict anxiety symptoms in humans and MEK/ERK inhibition dissociates innate and learned defensive behaviors in rats</atitle><jtitle>Molecular psychiatry</jtitle><stitle>Mol Psychiatry</stitle><addtitle>Mol Psychiatry</addtitle><date>2021-12-01</date><risdate>2021</risdate><volume>26</volume><issue>12</issue><spage>7257</spage><epage>7269</epage><pages>7257-7269</pages><issn>1359-4184</issn><eissn>1476-5578</eissn><abstract>We demonstrate that the rate of extracellular signal-related kinase phosphorylation (P-ERK1,2/Total-ERK1,2) in the amygdala is negatively and independently associated with anxiety symptoms in 23 consecutive patients with drug-resistant mesial temporal lobe epilepsy that was surgically treated. In naive Wistar rats, the P-ERK1,2/Total-ERK1,2 ratio in the amygdala correlates negatively with innate anxiety-related behavior on the elevated plus maze (
n
= 20) but positively with expression of defensive-learned behavior (i.e., freezing) on Pavlovian aversive (fear) conditioning (
n
= 29). The microinfusion of ERK1/2 inhibitor (FR180204,
n
= 8–13/group) or MEK inhibitor (U0126,
n
= 8–9/group) into the basolateral amygdala did not affect anxiety-related behavior but impaired the evocation (anticipation) of conditioned-defensive behavior (
n
= 9–11/group). In conclusion, the P-ERK1,2/Total-ERK1,2 ratio in the amygdala predicts anxiety in humans and the innate anxiety- and conditioned freezing behaviors in rats. However, the ERK1/2 in the basolateral AMY is only required for the expression of defensive-learned behavior. These results support a dissociate ERK-dependent mechanism in the amygdala between innate anxiety-like responses and the anticipation of learned-defensive behavior. These findings have implications for understanding highly prevalent psychiatric disorders related to the defensive circuit manifested by anxiety and fear.
Highlights
The P-ERK1,2/Total-ERK1,2 ratio in the amygdala (AMY) correlates negatively with anxiety symptoms in patients with mesial temporal lobe epilepsy.
The P-ERK1,2/Total-ERK1,2 in the amygdala correlates negatively with the anxiety-like behavior and positively with freezing-learned behavior in naive rats.
ERK1,2 in the basolateral amygdala is required for learned-defensive but not for the anxiety-like behavior expression in rats.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>34316004</pmid><doi>10.1038/s41380-021-01203-0</doi><tpages>13</tpages><orcidid>https://orcid.org/0000-0001-7526-1502</orcidid><orcidid>https://orcid.org/0000-0002-5401-7524</orcidid><orcidid>https://orcid.org/0000-0002-5513-8061</orcidid><orcidid>https://orcid.org/0000-0002-4435-6768</orcidid><orcidid>https://orcid.org/0000-0003-0523-4351</orcidid><orcidid>https://orcid.org/0000-0003-2536-6888</orcidid><orcidid>https://orcid.org/0000-0002-5292-8455</orcidid><orcidid>https://orcid.org/0000-0002-9875-6687</orcidid><orcidid>https://orcid.org/0000-0002-8152-7773</orcidid><orcidid>https://orcid.org/0000-0002-7547-6463</orcidid><orcidid>https://orcid.org/0000-0001-6905-5884</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1359-4184 |
| ispartof | Molecular psychiatry, 2021-12, Vol.26 (12), p.7257-7269 |
| issn | 1359-4184 1476-5578 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_2555965557 |
| source | MEDLINE; Springer Nature - Complete Springer Journals |
| subjects | 631/337 631/378 631/45 692/699/476 82/80 Amygdala Amygdala (Brain) Amygdala - metabolism Animals Anxiety Anxiety - metabolism Behavior Behavioral Sciences Biological Psychology Complications and side effects Defensive behavior Defensiveness (Psychology) Development and progression Drug resistance Epilepsy Extracellular signal-regulated kinase Fear Health aspects Humans Learning Medicine Medicine & Public Health MEK inhibitors Mental disorders Mitogen-Activated Protein Kinase 1 - antagonists & inhibitors Mitogen-Activated Protein Kinase 1 - metabolism Mitogen-Activated Protein Kinase 3 - antagonists & inhibitors Mitogen-Activated Protein Kinase 3 - metabolism Mitogen-Activated Protein Kinase Kinases - metabolism Neurosciences Pharmacotherapy Phosphorylation Physiological aspects Protein kinases Psychiatric research Psychiatry Rats Rats, Wistar Risk factors Rodents Temporal lobe Temporal lobe epilepsy Tonic immobility |
| title | The ERK phosphorylation levels in the amygdala predict anxiety symptoms in humans and MEK/ERK inhibition dissociates innate and learned defensive behaviors in rats |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-30T18%3A11%3A03IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_proqu&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=The%20ERK%20phosphorylation%20levels%20in%20the%20amygdala%20predict%20anxiety%20symptoms%20in%20humans%20and%20MEK/ERK%20inhibition%20dissociates%20innate%20and%20learned%20defensive%20behaviors%20in%20rats&rft.jtitle=Molecular%20psychiatry&rft.au=de%20Carvalho,%20Cristiane%20Ribeiro&rft.date=2021-12-01&rft.volume=26&rft.issue=12&rft.spage=7257&rft.epage=7269&rft.pages=7257-7269&rft.issn=1359-4184&rft.eissn=1476-5578&rft_id=info:doi/10.1038/s41380-021-01203-0&rft_dat=%3Cgale_proqu%3EA694903367%3C/gale_proqu%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2632488404&rft_id=info:pmid/34316004&rft_galeid=A694903367&rfr_iscdi=true |