Epigenetic Regulation of Glutamic Acid Decarboxylase 67 in a Hippocampal Circuit
GABAergic dysfunction in hippocampus, a key feature of schizophrenia (SZ), may contribute to cognitive impairment in this disorder. In stratum oriens (SO) of sector CA3/2 of the human hippocampus, a network of genes involved in the regulation of glutamic acid decarboxylase GAD67 has been identified....
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| Veröffentlicht in: | Cerebral cortex (New York, N.Y. 1991) N.Y. 1991), 2017-11, Vol.27 (11), p.5284-5293 |
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| creator | Subburaju, Sivan Coleman, Andrew J Cunningham, Miles G Ruzicka, W Brad Benes, Francine M |
| description | GABAergic dysfunction in hippocampus, a key feature of schizophrenia (SZ), may contribute to cognitive impairment in this disorder. In stratum oriens (SO) of sector CA3/2 of the human hippocampus, a network of genes involved in the regulation of glutamic acid decarboxylase GAD67 has been identified. Several of the genes in this network including epigenetic factors histone deacetylase 1 (HDAC1) and death-associated protein 6 (DAXX), the GABAergic enzyme GAD65 as well as the kainate receptor (KAR) subunits GluR6 and 7 show significant changes in expression in this area in SZ. We have tested whether HDAC1 and DAXX regulate GAD67, GAD65, or GluR in the intact rodent hippocampus. Stereotaxic injections of lentiviral vectors bearing shRNAi sequences for HDAC1 and DAXX were delivered into the SO of CA3/2, followed by laser microdissection of individual transduced GABA neurons. Quantitative PCR (QPCR) analyses demonstrated that inhibition of HDAC1 and DAXX increased expression of GAD67, GAD65, and GluR6 mRNA. Inhibition of DAXX, but not HDAC1 resulted in a significant increase in GluR7 mRNA. Our data support the hypothesis that HDAC1 and DAXX play a central role in coordinating the expression of genes in the GAD67 regulatory pathway in the SO of CA3/2. |
| doi_str_mv | 10.1093/cercor/bhw307 |
| format | Article |
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In stratum oriens (SO) of sector CA3/2 of the human hippocampus, a network of genes involved in the regulation of glutamic acid decarboxylase GAD67 has been identified. Several of the genes in this network including epigenetic factors histone deacetylase 1 (HDAC1) and death-associated protein 6 (DAXX), the GABAergic enzyme GAD65 as well as the kainate receptor (KAR) subunits GluR6 and 7 show significant changes in expression in this area in SZ. We have tested whether HDAC1 and DAXX regulate GAD67, GAD65, or GluR in the intact rodent hippocampus. Stereotaxic injections of lentiviral vectors bearing shRNAi sequences for HDAC1 and DAXX were delivered into the SO of CA3/2, followed by laser microdissection of individual transduced GABA neurons. Quantitative PCR (QPCR) analyses demonstrated that inhibition of HDAC1 and DAXX increased expression of GAD67, GAD65, and GluR6 mRNA. Inhibition of DAXX, but not HDAC1 resulted in a significant increase in GluR7 mRNA. Our data support the hypothesis that HDAC1 and DAXX play a central role in coordinating the expression of genes in the GAD67 regulatory pathway in the SO of CA3/2.</description><identifier>ISSN: 1047-3211</identifier><identifier>EISSN: 1460-2199</identifier><identifier>DOI: 10.1093/cercor/bhw307</identifier><identifier>PMID: 27733539</identifier><language>eng</language><publisher>United States: Oxford University Press</publisher><subject>Adaptor Proteins, Signal Transducing - antagonists & inhibitors ; Adaptor Proteins, Signal Transducing - metabolism ; Animals ; CA2 Region, Hippocampal - cytology ; CA2 Region, Hippocampal - metabolism ; CA3 Region, Hippocampal - cytology ; CA3 Region, Hippocampal - metabolism ; Cell Line ; Epigenesis, Genetic ; GABAergic Neurons - cytology ; GABAergic Neurons - metabolism ; Glutamate Decarboxylase - metabolism ; Histone Deacetylase 1 - antagonists & inhibitors ; Histone Deacetylase 1 - metabolism ; Male ; Molecular Chaperones ; Neural Pathways - cytology ; Neural Pathways - metabolism ; Nuclear Proteins - antagonists & inhibitors ; Nuclear Proteins - metabolism ; Original ; Rats, Sprague-Dawley ; Receptors, Glutamate - metabolism ; RNA, Messenger - metabolism</subject><ispartof>Cerebral cortex (New York, N.Y. 1991), 2017-11, Vol.27 (11), p.5284-5293</ispartof><rights>The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.</rights><rights>The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com 2016</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c387t-4ebd6501fb081de9245ffae77d7b016875eeccbdb1bde29fe2fb7304af3784673</citedby><cites>FETCH-LOGICAL-c387t-4ebd6501fb081de9245ffae77d7b016875eeccbdb1bde29fe2fb7304af3784673</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,776,780,881,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/27733539$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Subburaju, Sivan</creatorcontrib><creatorcontrib>Coleman, Andrew J</creatorcontrib><creatorcontrib>Cunningham, Miles G</creatorcontrib><creatorcontrib>Ruzicka, W Brad</creatorcontrib><creatorcontrib>Benes, Francine M</creatorcontrib><title>Epigenetic Regulation of Glutamic Acid Decarboxylase 67 in a Hippocampal Circuit</title><title>Cerebral cortex (New York, N.Y. 1991)</title><addtitle>Cereb Cortex</addtitle><description>GABAergic dysfunction in hippocampus, a key feature of schizophrenia (SZ), may contribute to cognitive impairment in this disorder. In stratum oriens (SO) of sector CA3/2 of the human hippocampus, a network of genes involved in the regulation of glutamic acid decarboxylase GAD67 has been identified. Several of the genes in this network including epigenetic factors histone deacetylase 1 (HDAC1) and death-associated protein 6 (DAXX), the GABAergic enzyme GAD65 as well as the kainate receptor (KAR) subunits GluR6 and 7 show significant changes in expression in this area in SZ. We have tested whether HDAC1 and DAXX regulate GAD67, GAD65, or GluR in the intact rodent hippocampus. Stereotaxic injections of lentiviral vectors bearing shRNAi sequences for HDAC1 and DAXX were delivered into the SO of CA3/2, followed by laser microdissection of individual transduced GABA neurons. Quantitative PCR (QPCR) analyses demonstrated that inhibition of HDAC1 and DAXX increased expression of GAD67, GAD65, and GluR6 mRNA. Inhibition of DAXX, but not HDAC1 resulted in a significant increase in GluR7 mRNA. Our data support the hypothesis that HDAC1 and DAXX play a central role in coordinating the expression of genes in the GAD67 regulatory pathway in the SO of CA3/2.</description><subject>Adaptor Proteins, Signal Transducing - antagonists & inhibitors</subject><subject>Adaptor Proteins, Signal Transducing - metabolism</subject><subject>Animals</subject><subject>CA2 Region, Hippocampal - cytology</subject><subject>CA2 Region, Hippocampal - metabolism</subject><subject>CA3 Region, Hippocampal - cytology</subject><subject>CA3 Region, Hippocampal - metabolism</subject><subject>Cell Line</subject><subject>Epigenesis, Genetic</subject><subject>GABAergic Neurons - cytology</subject><subject>GABAergic Neurons - metabolism</subject><subject>Glutamate Decarboxylase - metabolism</subject><subject>Histone Deacetylase 1 - antagonists & inhibitors</subject><subject>Histone Deacetylase 1 - metabolism</subject><subject>Male</subject><subject>Molecular Chaperones</subject><subject>Neural Pathways - cytology</subject><subject>Neural Pathways - metabolism</subject><subject>Nuclear Proteins - antagonists & inhibitors</subject><subject>Nuclear Proteins - metabolism</subject><subject>Original</subject><subject>Rats, Sprague-Dawley</subject><subject>Receptors, Glutamate - metabolism</subject><subject>RNA, Messenger - metabolism</subject><issn>1047-3211</issn><issn>1460-2199</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpVkc1LxDAQxYMo7rp69Co5eqmbNG3TXoRlXT9gQRE9hySdrJG2qUnrx39vpeuipxlmfrx5zEPolJILSgo21-C183P18sEI30NTmmQkimlR7A89SXjEYkon6CiEV0Ioj9P4EE1izhlLWTFFD6vWbqCBzmr8CJu-kp11DXYG31R9J-thvNC2xFegpVfu86uSAXDGsW2wxLe2bZ2WdSsrvLRe97Y7RgdGVgFOtnWGnq9XT8vbaH1_c7dcrCPNct5FCagySwk1iuS0hCJOUmMkcF5yRWiW8xRAa1UqqkqICwOxUZyRRBrG8yTjbIYuR922VzWUGprOy0q03tbSfwknrfi_aeyL2Lh3kSWUEkYHgfOtgHdvPYRO1DZoqCrZgOuDoDlLE5IWWTag0Yhq70LwYHZnKBE_KYgxBTGmMPBnf73t6N-3s29J1ob3</recordid><startdate>20171101</startdate><enddate>20171101</enddate><creator>Subburaju, Sivan</creator><creator>Coleman, Andrew J</creator><creator>Cunningham, Miles G</creator><creator>Ruzicka, W Brad</creator><creator>Benes, Francine M</creator><general>Oxford University Press</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>7X8</scope><scope>5PM</scope></search><sort><creationdate>20171101</creationdate><title>Epigenetic Regulation of Glutamic Acid Decarboxylase 67 in a Hippocampal Circuit</title><author>Subburaju, Sivan ; Coleman, Andrew J ; Cunningham, Miles G ; Ruzicka, W Brad ; Benes, Francine M</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c387t-4ebd6501fb081de9245ffae77d7b016875eeccbdb1bde29fe2fb7304af3784673</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>Adaptor Proteins, Signal Transducing - antagonists & inhibitors</topic><topic>Adaptor Proteins, Signal Transducing - metabolism</topic><topic>Animals</topic><topic>CA2 Region, Hippocampal - cytology</topic><topic>CA2 Region, Hippocampal - metabolism</topic><topic>CA3 Region, Hippocampal - cytology</topic><topic>CA3 Region, Hippocampal - metabolism</topic><topic>Cell Line</topic><topic>Epigenesis, Genetic</topic><topic>GABAergic Neurons - cytology</topic><topic>GABAergic Neurons - metabolism</topic><topic>Glutamate Decarboxylase - metabolism</topic><topic>Histone Deacetylase 1 - antagonists & inhibitors</topic><topic>Histone Deacetylase 1 - metabolism</topic><topic>Male</topic><topic>Molecular Chaperones</topic><topic>Neural Pathways - cytology</topic><topic>Neural Pathways - metabolism</topic><topic>Nuclear Proteins - antagonists & inhibitors</topic><topic>Nuclear Proteins - metabolism</topic><topic>Original</topic><topic>Rats, Sprague-Dawley</topic><topic>Receptors, Glutamate - metabolism</topic><topic>RNA, Messenger - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Subburaju, Sivan</creatorcontrib><creatorcontrib>Coleman, Andrew J</creatorcontrib><creatorcontrib>Cunningham, Miles G</creatorcontrib><creatorcontrib>Ruzicka, W Brad</creatorcontrib><creatorcontrib>Benes, Francine M</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Cerebral cortex (New York, N.Y. 1991)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Subburaju, Sivan</au><au>Coleman, Andrew J</au><au>Cunningham, Miles G</au><au>Ruzicka, W Brad</au><au>Benes, Francine M</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Epigenetic Regulation of Glutamic Acid Decarboxylase 67 in a Hippocampal Circuit</atitle><jtitle>Cerebral cortex (New York, N.Y. 1991)</jtitle><addtitle>Cereb Cortex</addtitle><date>2017-11-01</date><risdate>2017</risdate><volume>27</volume><issue>11</issue><spage>5284</spage><epage>5293</epage><pages>5284-5293</pages><issn>1047-3211</issn><eissn>1460-2199</eissn><abstract>GABAergic dysfunction in hippocampus, a key feature of schizophrenia (SZ), may contribute to cognitive impairment in this disorder. In stratum oriens (SO) of sector CA3/2 of the human hippocampus, a network of genes involved in the regulation of glutamic acid decarboxylase GAD67 has been identified. Several of the genes in this network including epigenetic factors histone deacetylase 1 (HDAC1) and death-associated protein 6 (DAXX), the GABAergic enzyme GAD65 as well as the kainate receptor (KAR) subunits GluR6 and 7 show significant changes in expression in this area in SZ. We have tested whether HDAC1 and DAXX regulate GAD67, GAD65, or GluR in the intact rodent hippocampus. Stereotaxic injections of lentiviral vectors bearing shRNAi sequences for HDAC1 and DAXX were delivered into the SO of CA3/2, followed by laser microdissection of individual transduced GABA neurons. Quantitative PCR (QPCR) analyses demonstrated that inhibition of HDAC1 and DAXX increased expression of GAD67, GAD65, and GluR6 mRNA. Inhibition of DAXX, but not HDAC1 resulted in a significant increase in GluR7 mRNA. 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| source | Oxford University Press Journals All Titles (1996-Current); MEDLINE; EZB-FREE-00999 freely available EZB journals; Alma/SFX Local Collection |
| subjects | Adaptor Proteins, Signal Transducing - antagonists & inhibitors Adaptor Proteins, Signal Transducing - metabolism Animals CA2 Region, Hippocampal - cytology CA2 Region, Hippocampal - metabolism CA3 Region, Hippocampal - cytology CA3 Region, Hippocampal - metabolism Cell Line Epigenesis, Genetic GABAergic Neurons - cytology GABAergic Neurons - metabolism Glutamate Decarboxylase - metabolism Histone Deacetylase 1 - antagonists & inhibitors Histone Deacetylase 1 - metabolism Male Molecular Chaperones Neural Pathways - cytology Neural Pathways - metabolism Nuclear Proteins - antagonists & inhibitors Nuclear Proteins - metabolism Original Rats, Sprague-Dawley Receptors, Glutamate - metabolism RNA, Messenger - metabolism |
| title | Epigenetic Regulation of Glutamic Acid Decarboxylase 67 in a Hippocampal Circuit |
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