Effects of a phosphodiesterase IV inhibitor rolipram on microsphere embolism‐induced defects in memory function and cerebral cyclic AMP signal transduction system in rats
The effects of treatment with rolipram, a specific phosphodiesterase IV inhibitor, on learning and memory function and on the cyclic AMP/PKA/CREB signal transduction system were examined in rats with microsphere embolism (ME)‐induced cerebral ischaemia. Sustained cerebral ischaemia was induced by th...
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description | The effects of treatment with rolipram, a specific phosphodiesterase IV inhibitor, on learning and memory function and on the cyclic AMP/PKA/CREB signal transduction system were examined in rats with microsphere embolism (ME)‐induced cerebral ischaemia.
Sustained cerebral ischaemia was induced by the injection of 900 microspheres (48 μm in diameter) into the right hemisphere of the rat brain. The animals were treated once daily with 3 mg kg−1 rolipram i.p. from 6 h after the onset of the operation for consecutive 10 days.
Microsphere‐embolized rats showed prolongation of the escape latency in the water maze task starting from day 7 after the operation and lasting for 3 consecutive days. Treatment with rolipram reduced the escape latency.
ME decreased the cyclic AMP content, cytosolic PKA Cβ level, and nuclear PKA Cα and Cβ levels, as well as reduced the pCREB level and the DNA‐binding activity of CREB in the cerebral cortex and hippocampus on day 10 after the operation. These alterations were attenuated by treatment with rolipram.
These results suggest that ME‐induced failure in learning and memory function may be mediated by dysfunction of the cyclic AMP/PKA/CREB signal transduction system, that rolipram may ameliorate ME‐induced impairment of learning and memory function, and that the drug effect may be partly attributed to activation of the cyclic AMP/PKA/CREB signal transduction system.
British Journal of Pharmacology (2002) 135, 1783–1793; doi:10.1038/sj.bjp.0704629 |
doi_str_mv | 10.1038/sj.bjp.0704629 |
format | Article |
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Sustained cerebral ischaemia was induced by the injection of 900 microspheres (48 μm in diameter) into the right hemisphere of the rat brain. The animals were treated once daily with 3 mg kg−1 rolipram i.p. from 6 h after the onset of the operation for consecutive 10 days.
Microsphere‐embolized rats showed prolongation of the escape latency in the water maze task starting from day 7 after the operation and lasting for 3 consecutive days. Treatment with rolipram reduced the escape latency.
ME decreased the cyclic AMP content, cytosolic PKA Cβ level, and nuclear PKA Cα and Cβ levels, as well as reduced the pCREB level and the DNA‐binding activity of CREB in the cerebral cortex and hippocampus on day 10 after the operation. These alterations were attenuated by treatment with rolipram.
These results suggest that ME‐induced failure in learning and memory function may be mediated by dysfunction of the cyclic AMP/PKA/CREB signal transduction system, that rolipram may ameliorate ME‐induced impairment of learning and memory function, and that the drug effect may be partly attributed to activation of the cyclic AMP/PKA/CREB signal transduction system.
British Journal of Pharmacology (2002) 135, 1783–1793; doi:10.1038/sj.bjp.0704629</description><identifier>ISSN: 0007-1188</identifier><identifier>EISSN: 1476-5381</identifier><identifier>DOI: 10.1038/sj.bjp.0704629</identifier><identifier>PMID: 11934820</identifier><identifier>CODEN: BJPCBM</identifier><language>eng</language><publisher>Oxford, UK: Blackwell Publishing Ltd</publisher><subject>3',5'-Cyclic-AMP Phosphodiesterases - drug effects ; 3',5'-Cyclic-AMP Phosphodiesterases - metabolism ; Animals ; Binding Sites ; Biological and medical sciences ; Brain Ischemia - etiology ; Brain Ischemia - metabolism ; Brain Ischemia - prevention & control ; Cell Nucleus - drug effects ; Cell Nucleus - metabolism ; Cyclic AMP - metabolism ; Cyclic AMP Response Element-Binding Protein - drug effects ; Cyclic AMP Response Element-Binding Protein - metabolism ; Cyclic AMP-Dependent Protein Kinases - metabolism ; cyclic AMP/PKA/CREB signal transduction system ; Cyclic Nucleotide Phosphodiesterases, Type 4 ; Cytosol - drug effects ; Cytosol - metabolism ; Embolism - complications ; learning and memory ; Male ; Medical sciences ; Memory - drug effects ; microsphere embolism ; Microspheres ; Phosphodiesterase Inhibitors - pharmacology ; Phosphodiesterase Inhibitors - therapeutic use ; Protein Subunits ; Rats ; Rats, Wistar ; Rolipram ; Rolipram - pharmacology ; Rolipram - therapeutic use ; Signal Transduction - drug effects</subject><ispartof>British journal of pharmacology, 2002-04, Vol.135 (7), p.1783-1793</ispartof><rights>2002 British Pharmacological Society</rights><rights>2003 INIST-CNRS</rights><rights>Copyright Nature Publishing Group Apr 2002</rights><rights>Copyright 2002, Nature Publishing Group 2002 Nature Publishing Group</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c5532-83aac07bbc40a42e9a014581f81a3c1acddeaf65242161c53570b446aeae86983</citedby><cites>FETCH-LOGICAL-c5532-83aac07bbc40a42e9a014581f81a3c1acddeaf65242161c53570b446aeae86983</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC1573294/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC1573294/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,314,727,780,784,885,1417,1433,27924,27925,45574,45575,46409,46833,53791,53793</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=14992694$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/11934820$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Nagakura, Akira</creatorcontrib><creatorcontrib>Niimura, Makiko</creatorcontrib><creatorcontrib>Takeo, Satoshi</creatorcontrib><title>Effects of a phosphodiesterase IV inhibitor rolipram on microsphere embolism‐induced defects in memory function and cerebral cyclic AMP signal transduction system in rats</title><title>British journal of pharmacology</title><addtitle>Br J Pharmacol</addtitle><description>The effects of treatment with rolipram, a specific phosphodiesterase IV inhibitor, on learning and memory function and on the cyclic AMP/PKA/CREB signal transduction system were examined in rats with microsphere embolism (ME)‐induced cerebral ischaemia.
Sustained cerebral ischaemia was induced by the injection of 900 microspheres (48 μm in diameter) into the right hemisphere of the rat brain. The animals were treated once daily with 3 mg kg−1 rolipram i.p. from 6 h after the onset of the operation for consecutive 10 days.
Microsphere‐embolized rats showed prolongation of the escape latency in the water maze task starting from day 7 after the operation and lasting for 3 consecutive days. Treatment with rolipram reduced the escape latency.
ME decreased the cyclic AMP content, cytosolic PKA Cβ level, and nuclear PKA Cα and Cβ levels, as well as reduced the pCREB level and the DNA‐binding activity of CREB in the cerebral cortex and hippocampus on day 10 after the operation. These alterations were attenuated by treatment with rolipram.
These results suggest that ME‐induced failure in learning and memory function may be mediated by dysfunction of the cyclic AMP/PKA/CREB signal transduction system, that rolipram may ameliorate ME‐induced impairment of learning and memory function, and that the drug effect may be partly attributed to activation of the cyclic AMP/PKA/CREB signal transduction system.
British Journal of Pharmacology (2002) 135, 1783–1793; doi:10.1038/sj.bjp.0704629</description><subject>3',5'-Cyclic-AMP Phosphodiesterases - drug effects</subject><subject>3',5'-Cyclic-AMP Phosphodiesterases - metabolism</subject><subject>Animals</subject><subject>Binding Sites</subject><subject>Biological and medical sciences</subject><subject>Brain Ischemia - etiology</subject><subject>Brain Ischemia - metabolism</subject><subject>Brain Ischemia - prevention & control</subject><subject>Cell Nucleus - drug effects</subject><subject>Cell Nucleus - metabolism</subject><subject>Cyclic AMP - metabolism</subject><subject>Cyclic AMP Response Element-Binding Protein - drug effects</subject><subject>Cyclic AMP Response Element-Binding Protein - metabolism</subject><subject>Cyclic AMP-Dependent Protein Kinases - metabolism</subject><subject>cyclic AMP/PKA/CREB signal transduction system</subject><subject>Cyclic Nucleotide Phosphodiesterases, Type 4</subject><subject>Cytosol - drug effects</subject><subject>Cytosol - metabolism</subject><subject>Embolism - complications</subject><subject>learning and memory</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Memory - drug effects</subject><subject>microsphere embolism</subject><subject>Microspheres</subject><subject>Phosphodiesterase Inhibitors - pharmacology</subject><subject>Phosphodiesterase Inhibitors - therapeutic use</subject><subject>Protein Subunits</subject><subject>Rats</subject><subject>Rats, Wistar</subject><subject>Rolipram</subject><subject>Rolipram - pharmacology</subject><subject>Rolipram - therapeutic use</subject><subject>Signal Transduction - drug effects</subject><issn>0007-1188</issn><issn>1476-5381</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2002</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><recordid>eNqFks9u1DAQxiMEokvhyhFZSHDL4n9JnAtSWxVaqYgegKs1cSZdr5J4sRPQ3ngEHoSn4kmY7a4ocOFgWfL85vPMN5NlTwVfCq7Mq7ReNuvNkldcl7K-ly2Ersq8UEbczxac8yoXwpij7FFKa84pWBUPsyMhaqWN5Ivsx3nXoZsSCx0DtlmFRKf1mCaMkJBdfmJ-XPnGTyGyGHq_iTCwMLLBu7iDMSLDoaFIGn5---7HdnbYshb3sp5IHELcsm4e3eQpE8aWOUprIvTMbV3vHTt5d82SvxnpZYowJhK5ZdOWChl2KhGm9Dh70EGf8MnhPs4-vjn_cHaRX71_e3l2cpW7olAyNwrA8appnOagJdZAjRdGdEaAcgJc2yJ0ZSG1FKVwhSoq3mhdAgKasjbqOHu9193MzYCtw5GK6u0m-gHi1gbw9u_I6Ff2JnyxoqiUrDUJvDwIxPB5JjPt4JPDvocRw5xsRaA0hSDw-T_gOsyRbEhWioomJwwnaLmHdo6niN3vSgS3uy2waW1pC-xhCyjh2Z_13-GHsRPw4gBActB3ZLnz6Y7TdS3L2z7Unvvqe9z-51t7en2hhZbqF_Il0ag</recordid><startdate>200204</startdate><enddate>200204</enddate><creator>Nagakura, Akira</creator><creator>Niimura, Makiko</creator><creator>Takeo, Satoshi</creator><general>Blackwell Publishing Ltd</general><general>Nature Publishing</general><scope>IQODW</scope><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>7QP</scope><scope>7RV</scope><scope>7TK</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</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>M7P</scope><scope>NAPCQ</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>200204</creationdate><title>Effects of a phosphodiesterase IV inhibitor rolipram on microsphere embolism‐induced defects in memory function and cerebral cyclic AMP signal transduction system in rats</title><author>Nagakura, Akira ; Niimura, Makiko ; Takeo, Satoshi</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c5532-83aac07bbc40a42e9a014581f81a3c1acddeaf65242161c53570b446aeae86983</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2002</creationdate><topic>3',5'-Cyclic-AMP Phosphodiesterases - drug effects</topic><topic>3',5'-Cyclic-AMP Phosphodiesterases - metabolism</topic><topic>Animals</topic><topic>Binding Sites</topic><topic>Biological and medical sciences</topic><topic>Brain Ischemia - etiology</topic><topic>Brain Ischemia - metabolism</topic><topic>Brain Ischemia - prevention & control</topic><topic>Cell Nucleus - drug effects</topic><topic>Cell Nucleus - metabolism</topic><topic>Cyclic AMP - metabolism</topic><topic>Cyclic AMP Response Element-Binding Protein - drug effects</topic><topic>Cyclic AMP Response Element-Binding Protein - metabolism</topic><topic>Cyclic AMP-Dependent Protein Kinases - metabolism</topic><topic>cyclic AMP/PKA/CREB signal transduction system</topic><topic>Cyclic Nucleotide Phosphodiesterases, Type 4</topic><topic>Cytosol - drug effects</topic><topic>Cytosol - metabolism</topic><topic>Embolism - complications</topic><topic>learning and memory</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Memory - drug effects</topic><topic>microsphere embolism</topic><topic>Microspheres</topic><topic>Phosphodiesterase Inhibitors - pharmacology</topic><topic>Phosphodiesterase Inhibitors - therapeutic use</topic><topic>Protein Subunits</topic><topic>Rats</topic><topic>Rats, Wistar</topic><topic>Rolipram</topic><topic>Rolipram - pharmacology</topic><topic>Rolipram - therapeutic use</topic><topic>Signal Transduction - drug effects</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Nagakura, Akira</creatorcontrib><creatorcontrib>Niimura, Makiko</creatorcontrib><creatorcontrib>Takeo, Satoshi</creatorcontrib><collection>Pascal-Francis</collection><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>Calcium & Calcified Tissue Abstracts</collection><collection>Nursing & Allied Health Database</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>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>Biological Science Database</collection><collection>Nursing & Allied Health Premium</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>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>British journal of pharmacology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Nagakura, Akira</au><au>Niimura, Makiko</au><au>Takeo, Satoshi</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Effects of a phosphodiesterase IV inhibitor rolipram on microsphere embolism‐induced defects in memory function and cerebral cyclic AMP signal transduction system in rats</atitle><jtitle>British journal of pharmacology</jtitle><addtitle>Br J Pharmacol</addtitle><date>2002-04</date><risdate>2002</risdate><volume>135</volume><issue>7</issue><spage>1783</spage><epage>1793</epage><pages>1783-1793</pages><issn>0007-1188</issn><eissn>1476-5381</eissn><coden>BJPCBM</coden><abstract>The effects of treatment with rolipram, a specific phosphodiesterase IV inhibitor, on learning and memory function and on the cyclic AMP/PKA/CREB signal transduction system were examined in rats with microsphere embolism (ME)‐induced cerebral ischaemia.
Sustained cerebral ischaemia was induced by the injection of 900 microspheres (48 μm in diameter) into the right hemisphere of the rat brain. The animals were treated once daily with 3 mg kg−1 rolipram i.p. from 6 h after the onset of the operation for consecutive 10 days.
Microsphere‐embolized rats showed prolongation of the escape latency in the water maze task starting from day 7 after the operation and lasting for 3 consecutive days. Treatment with rolipram reduced the escape latency.
ME decreased the cyclic AMP content, cytosolic PKA Cβ level, and nuclear PKA Cα and Cβ levels, as well as reduced the pCREB level and the DNA‐binding activity of CREB in the cerebral cortex and hippocampus on day 10 after the operation. These alterations were attenuated by treatment with rolipram.
These results suggest that ME‐induced failure in learning and memory function may be mediated by dysfunction of the cyclic AMP/PKA/CREB signal transduction system, that rolipram may ameliorate ME‐induced impairment of learning and memory function, and that the drug effect may be partly attributed to activation of the cyclic AMP/PKA/CREB signal transduction system.
British Journal of Pharmacology (2002) 135, 1783–1793; doi:10.1038/sj.bjp.0704629</abstract><cop>Oxford, UK</cop><pub>Blackwell Publishing Ltd</pub><pmid>11934820</pmid><doi>10.1038/sj.bjp.0704629</doi><tpages>11</tpages><oa>free_for_read</oa></addata></record> |
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subjects | 3',5'-Cyclic-AMP Phosphodiesterases - drug effects 3',5'-Cyclic-AMP Phosphodiesterases - metabolism Animals Binding Sites Biological and medical sciences Brain Ischemia - etiology Brain Ischemia - metabolism Brain Ischemia - prevention & control Cell Nucleus - drug effects Cell Nucleus - metabolism Cyclic AMP - metabolism Cyclic AMP Response Element-Binding Protein - drug effects Cyclic AMP Response Element-Binding Protein - metabolism Cyclic AMP-Dependent Protein Kinases - metabolism cyclic AMP/PKA/CREB signal transduction system Cyclic Nucleotide Phosphodiesterases, Type 4 Cytosol - drug effects Cytosol - metabolism Embolism - complications learning and memory Male Medical sciences Memory - drug effects microsphere embolism Microspheres Phosphodiesterase Inhibitors - pharmacology Phosphodiesterase Inhibitors - therapeutic use Protein Subunits Rats Rats, Wistar Rolipram Rolipram - pharmacology Rolipram - therapeutic use Signal Transduction - drug effects |
title | Effects of a phosphodiesterase IV inhibitor rolipram on microsphere embolism‐induced defects in memory function and cerebral cyclic AMP signal transduction system in rats |
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