Estradiol Alters Only GAD67 mRNA Levels in Ischemic Rat Brain with No Consequent Effects on GABA
The present study tested the hypothesis that estradiol reduces tissue infarction after middle cerebral artery occlusion (MCAO) in estradiol-deficient females by augmenting glutamic acid decarboxylase (GAD) expression and thus activity, leading to increases in γ-amino-butyric acid (GABA) tissue level...
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| Veröffentlicht in: | Journal of cerebral blood flow and metabolism 2006-04, Vol.26 (4), p.518-526 |
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| container_title | Journal of cerebral blood flow and metabolism |
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| creator | Joh, Hung-Dong Searles, Robin V Selmanoff, Michael Alkayed, Nabil J Koehler, Raymond C Hurn, Patricia D Murphy, Stephanie J |
| description | The present study tested the hypothesis that estradiol reduces tissue infarction after middle cerebral artery occlusion (MCAO) in estradiol-deficient females by augmenting glutamic acid decarboxylase (GAD) expression and thus activity, leading to increases in γ-amino-butyric acid (GABA) tissue levels. Glutamic acid decarboxylase is the principal enzyme for GABA synthesis and has two isoforms, GAD65 and GAD67, which differ in size and cellular distribution. Rats were ovariectomized 7 to 8 days before receiving no hormone, placebo, or 25 μg estradiol via subcutaneous implant 7 to 10 days before harvesting tissue in either ischemic cohorts after 2 h of MCAO (end-ischemia) or in nonischemic cohorts. Selected cortical and striatal regions were microdissected from harvested brains. GAD65/67 mRNA levels were determined by microlysate ribonuclease protection assay. End-ischemic GABA concentrations were determined by HPLC. Steroid treatment selectively decreased ischemic cortical GAD67 mRNA levels. In most brain regions evaluated, regional GABA concentrations increased with ischemia regardless of treatment. Estradiol blocked MCAO-induced increases in GABA concentration only in dorsomedial cortex. These data suggest that estradiol repletion in ischemic rat brain selectively decreases GAD67 mRNA levels but does not alter steady-state GABA concentrations. It may be that estradiol under ischemic conditions is attenuating GABA metabolism rather than enhancing synthesis or is augmenting other aspects of GABAergic transmission such as GABA transporters and receptors. |
| doi_str_mv | 10.1038/sj.jcbfm.9600211 |
| format | Article |
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Glutamic acid decarboxylase is the principal enzyme for GABA synthesis and has two isoforms, GAD65 and GAD67, which differ in size and cellular distribution. Rats were ovariectomized 7 to 8 days before receiving no hormone, placebo, or 25 μg estradiol via subcutaneous implant 7 to 10 days before harvesting tissue in either ischemic cohorts after 2 h of MCAO (end-ischemia) or in nonischemic cohorts. Selected cortical and striatal regions were microdissected from harvested brains. GAD65/67 mRNA levels were determined by microlysate ribonuclease protection assay. End-ischemic GABA concentrations were determined by HPLC. Steroid treatment selectively decreased ischemic cortical GAD67 mRNA levels. In most brain regions evaluated, regional GABA concentrations increased with ischemia regardless of treatment. Estradiol blocked MCAO-induced increases in GABA concentration only in dorsomedial cortex. These data suggest that estradiol repletion in ischemic rat brain selectively decreases GAD67 mRNA levels but does not alter steady-state GABA concentrations. It may be that estradiol under ischemic conditions is attenuating GABA metabolism rather than enhancing synthesis or is augmenting other aspects of GABAergic transmission such as GABA transporters and receptors.</description><identifier>ISSN: 0271-678X</identifier><identifier>EISSN: 1559-7016</identifier><identifier>DOI: 10.1038/sj.jcbfm.9600211</identifier><identifier>PMID: 16094313</identifier><identifier>CODEN: JCBMDN</identifier><language>eng</language><publisher>London, England: SAGE Publications</publisher><subject>Animals ; Biological and medical sciences ; Blood. Blood coagulation. Reticuloendothelial system ; Brain Chemistry ; Brain Ischemia - metabolism ; Cerebral Cortex - chemistry ; Corpus Striatum - chemistry ; Estradiol - deficiency ; Estradiol - pharmacology ; Female ; gamma-Aminobutyric Acid - drug effects ; Glutamate Decarboxylase - drug effects ; Glutamate Decarboxylase - genetics ; Infarction, Middle Cerebral Artery ; Isoenzymes - drug effects ; Isoenzymes - genetics ; Medical sciences ; Neurology ; Neuropharmacology ; Neuroprotective agent ; Ovariectomy ; Pharmacology. Drug treatments ; Rats ; Rats, Wistar ; RNA, Messenger - analysis ; RNA, Messenger - drug effects ; Vascular diseases and vascular malformations of the nervous system</subject><ispartof>Journal of cerebral blood flow and metabolism, 2006-04, Vol.26 (4), p.518-526</ispartof><rights>2006 ISCBFM</rights><rights>2006 INIST-CNRS</rights><rights>Copyright Nature Publishing Group Apr 2006</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://journals.sagepub.com/doi/pdf/10.1038/sj.jcbfm.9600211$$EPDF$$P50$$Gsage$$H</linktopdf><linktohtml>$$Uhttps://journals.sagepub.com/doi/10.1038/sj.jcbfm.9600211$$EHTML$$P50$$Gsage$$H</linktohtml><link.rule.ids>230,314,776,780,881,21798,27901,27902,43597,43598</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=17660358$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/16094313$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Joh, Hung-Dong</creatorcontrib><creatorcontrib>Searles, Robin V</creatorcontrib><creatorcontrib>Selmanoff, Michael</creatorcontrib><creatorcontrib>Alkayed, Nabil J</creatorcontrib><creatorcontrib>Koehler, Raymond C</creatorcontrib><creatorcontrib>Hurn, Patricia D</creatorcontrib><creatorcontrib>Murphy, Stephanie J</creatorcontrib><title>Estradiol Alters Only GAD67 mRNA Levels in Ischemic Rat Brain with No Consequent Effects on GABA</title><title>Journal of cerebral blood flow and metabolism</title><addtitle>J Cereb Blood Flow Metab</addtitle><description>The present study tested the hypothesis that estradiol reduces tissue infarction after middle cerebral artery occlusion (MCAO) in estradiol-deficient females by augmenting glutamic acid decarboxylase (GAD) expression and thus activity, leading to increases in γ-amino-butyric acid (GABA) tissue levels. Glutamic acid decarboxylase is the principal enzyme for GABA synthesis and has two isoforms, GAD65 and GAD67, which differ in size and cellular distribution. Rats were ovariectomized 7 to 8 days before receiving no hormone, placebo, or 25 μg estradiol via subcutaneous implant 7 to 10 days before harvesting tissue in either ischemic cohorts after 2 h of MCAO (end-ischemia) or in nonischemic cohorts. Selected cortical and striatal regions were microdissected from harvested brains. GAD65/67 mRNA levels were determined by microlysate ribonuclease protection assay. End-ischemic GABA concentrations were determined by HPLC. Steroid treatment selectively decreased ischemic cortical GAD67 mRNA levels. In most brain regions evaluated, regional GABA concentrations increased with ischemia regardless of treatment. Estradiol blocked MCAO-induced increases in GABA concentration only in dorsomedial cortex. These data suggest that estradiol repletion in ischemic rat brain selectively decreases GAD67 mRNA levels but does not alter steady-state GABA concentrations. It may be that estradiol under ischemic conditions is attenuating GABA metabolism rather than enhancing synthesis or is augmenting other aspects of GABAergic transmission such as GABA transporters and receptors.</description><subject>Animals</subject><subject>Biological and medical sciences</subject><subject>Blood. Blood coagulation. Reticuloendothelial system</subject><subject>Brain Chemistry</subject><subject>Brain Ischemia - metabolism</subject><subject>Cerebral Cortex - chemistry</subject><subject>Corpus Striatum - chemistry</subject><subject>Estradiol - deficiency</subject><subject>Estradiol - pharmacology</subject><subject>Female</subject><subject>gamma-Aminobutyric Acid - drug effects</subject><subject>Glutamate Decarboxylase - drug effects</subject><subject>Glutamate Decarboxylase - genetics</subject><subject>Infarction, Middle Cerebral Artery</subject><subject>Isoenzymes - drug effects</subject><subject>Isoenzymes - genetics</subject><subject>Medical sciences</subject><subject>Neurology</subject><subject>Neuropharmacology</subject><subject>Neuroprotective agent</subject><subject>Ovariectomy</subject><subject>Pharmacology. Drug treatments</subject><subject>Rats</subject><subject>Rats, Wistar</subject><subject>RNA, Messenger - analysis</subject><subject>RNA, Messenger - drug effects</subject><subject>Vascular diseases and vascular malformations of the nervous system</subject><issn>0271-678X</issn><issn>1559-7016</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2006</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNpdkt1rFDEUxYModlt990mCYN9mzZ1MPuZFmK5rLSwtFAXfYjabdDNkMmsyW-l_b2pXq-YlkPPj5NzLQegVkDkQKt_lft6btRvmLSekBniCZsBYWwkC_CmakVpAxYX8eoSOc-4JIZIy9hwdASdtQ4HO0LdlnpLe-DHgLkw2ZXwVwx0-7z5wgYfryw6v7K0NGfuIL7LZ2sEbfK0nfJZ0efrhpy2-HPFijNl-39s44aVz1kwZj7G4nHUv0DOnQ7YvD_cJ-vJx-XnxqVpdnV8sulW1o8Ch0kxSwcDJWruWCFE7y9cgGZBmIzYcAFyROWVUcCbqWjdcaFOEtRaWF-EEvX_w3e3Xg92YEiXpoHbJDzrdqVF79a8S_VbdjLcKGiASZDE4PRiksUySJzX4bGwIOtpxnxUX5ciGFPDNf2A_7lMsw6ka2kYSkHWBXv8d50-O35svwNsDoLPRwSUdjc-PnOCcUHYfq3rgsr6xjz8BUfcNULlXvxqgDg2gPwHjIJ9d</recordid><startdate>200604</startdate><enddate>200604</enddate><creator>Joh, Hung-Dong</creator><creator>Searles, Robin V</creator><creator>Selmanoff, Michael</creator><creator>Alkayed, Nabil J</creator><creator>Koehler, Raymond C</creator><creator>Hurn, Patricia D</creator><creator>Murphy, Stephanie J</creator><general>SAGE Publications</general><general>Lippincott Williams & Wilkins</general><general>Sage Publications Ltd</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>3V.</scope><scope>7X7</scope><scope>7XB</scope><scope>88A</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>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>200604</creationdate><title>Estradiol Alters Only GAD67 mRNA Levels in Ischemic Rat Brain with No Consequent Effects on GABA</title><author>Joh, Hung-Dong ; Searles, Robin V ; Selmanoff, Michael ; Alkayed, Nabil J ; Koehler, Raymond C ; Hurn, Patricia D ; Murphy, Stephanie J</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-p3161-a583751f82af90772fe6b185104d7d6111f7516353765722a467acd61ba7e6163</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2006</creationdate><topic>Animals</topic><topic>Biological and medical sciences</topic><topic>Blood. Blood coagulation. Reticuloendothelial system</topic><topic>Brain Chemistry</topic><topic>Brain Ischemia - metabolism</topic><topic>Cerebral Cortex - chemistry</topic><topic>Corpus Striatum - chemistry</topic><topic>Estradiol - deficiency</topic><topic>Estradiol - pharmacology</topic><topic>Female</topic><topic>gamma-Aminobutyric Acid - drug effects</topic><topic>Glutamate Decarboxylase - drug effects</topic><topic>Glutamate Decarboxylase - genetics</topic><topic>Infarction, Middle Cerebral Artery</topic><topic>Isoenzymes - drug effects</topic><topic>Isoenzymes - genetics</topic><topic>Medical sciences</topic><topic>Neurology</topic><topic>Neuropharmacology</topic><topic>Neuroprotective agent</topic><topic>Ovariectomy</topic><topic>Pharmacology. 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Glutamic acid decarboxylase is the principal enzyme for GABA synthesis and has two isoforms, GAD65 and GAD67, which differ in size and cellular distribution. Rats were ovariectomized 7 to 8 days before receiving no hormone, placebo, or 25 μg estradiol via subcutaneous implant 7 to 10 days before harvesting tissue in either ischemic cohorts after 2 h of MCAO (end-ischemia) or in nonischemic cohorts. Selected cortical and striatal regions were microdissected from harvested brains. GAD65/67 mRNA levels were determined by microlysate ribonuclease protection assay. End-ischemic GABA concentrations were determined by HPLC. Steroid treatment selectively decreased ischemic cortical GAD67 mRNA levels. In most brain regions evaluated, regional GABA concentrations increased with ischemia regardless of treatment. Estradiol blocked MCAO-induced increases in GABA concentration only in dorsomedial cortex. These data suggest that estradiol repletion in ischemic rat brain selectively decreases GAD67 mRNA levels but does not alter steady-state GABA concentrations. It may be that estradiol under ischemic conditions is attenuating GABA metabolism rather than enhancing synthesis or is augmenting other aspects of GABAergic transmission such as GABA transporters and receptors.</abstract><cop>London, England</cop><pub>SAGE Publications</pub><pmid>16094313</pmid><doi>10.1038/sj.jcbfm.9600211</doi><tpages>9</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Animals Biological and medical sciences Blood. Blood coagulation. Reticuloendothelial system Brain Chemistry Brain Ischemia - metabolism Cerebral Cortex - chemistry Corpus Striatum - chemistry Estradiol - deficiency Estradiol - pharmacology Female gamma-Aminobutyric Acid - drug effects Glutamate Decarboxylase - drug effects Glutamate Decarboxylase - genetics Infarction, Middle Cerebral Artery Isoenzymes - drug effects Isoenzymes - genetics Medical sciences Neurology Neuropharmacology Neuroprotective agent Ovariectomy Pharmacology. Drug treatments Rats Rats, Wistar RNA, Messenger - analysis RNA, Messenger - drug effects Vascular diseases and vascular malformations of the nervous system |
| title | Estradiol Alters Only GAD67 mRNA Levels in Ischemic Rat Brain with No Consequent Effects on GABA |
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