Rapid and profound rewiring of brain lipid signaling networks by acute diacylglycerol lipase inhibition
Diacylglycerol lipases (DAGLα and DAGLβ) convert diacylglycerol to the endocannabinoid 2-arachidonoylglycerol. Our understanding of DAGL function has been hindered by a lack of chemical probes that can perturb these enzymes in vivo. Here, we report a set of centrally active DAGL inhibitors and a str...
Gespeichert in:
| Veröffentlicht in: | Proceedings of the National Academy of Sciences - PNAS 2016-01, Vol.113 (1), p.26-33 |
|---|---|
| Hauptverfasser: | , , , , , , , , , , , , , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 33 |
|---|---|
| container_issue | 1 |
| container_start_page | 26 |
| container_title | Proceedings of the National Academy of Sciences - PNAS |
| container_volume | 113 |
| creator | Ogasawara, Daisuke Deng, Hui Viader, Andreu Baggelaar, Marc P. Breman, Arjen den Dulk, Hans van den Nieuwendijk, Adrianus M. C. H. Soethoudt, Marjolein van der Wel, Tom Zhou, Juan Overkleeft, Herman S. Sanchez-Alavez, Manuel Mori, Simone Nguyen, William Conti, Bruno Liu, Xiaojie Chen, Yao Liu, Qing-song Cravatt, Benjamin F. van der Stelt, Mario |
| description | Diacylglycerol lipases (DAGLα and DAGLβ) convert diacylglycerol to the endocannabinoid 2-arachidonoylglycerol. Our understanding of DAGL function has been hindered by a lack of chemical probes that can perturb these enzymes in vivo. Here, we report a set of centrally active DAGL inhibitors and a structurally related control probe and their use, in combination with chemical proteomics and lipidomics, to determine the impact of acute DAGL blockade on brain lipid networks in mice. Within 2 h, DAGL inhibition produced a striking reorganization of bioactive lipids, including elevations in DAGs and reductions in endocannabinoids and eicosanoids. We also found that DAGLα is a short half-life protein, and the inactivation of DAGLs disrupts cannabinoid receptor-dependent synaptic plasticity and impairs neuroinflammatory responses, including lipopolysaccharide-induced anapyrexia. These findings illuminate the highly interconnected and dynamic nature of lipid signaling pathways in the brain and the central role that DAGL enzymes play in regulating this network. |
| doi_str_mv | 10.1073/pnas.1522364112 |
| format | Article |
| fullrecord | <record><control><sourceid>jstor_proqu</sourceid><recordid>TN_cdi_proquest_miscellaneous_1837310716</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><jstor_id>26467284</jstor_id><sourcerecordid>26467284</sourcerecordid><originalsourceid>FETCH-LOGICAL-c563t-6bea3362d25a3a2cff6d91a00dd2b34926892da716911c36ce113504e5b9e5963</originalsourceid><addsrcrecordid>eNqFkc2L1TAUxYMoznN07UYl4MZNZ3Lz1WQjyOAXDAii65CmaSfPvqQmrcP77219z-foxlUC53dObu5B6CmQCyA1uxyjLRcgKGWSA9B7aANEQyW5JvfRhhBaV4pTfoYelbIlhGihyEN0RqWUigm1Qf1nO4YW29jiMacuzcsl-9uQQ-xx6nCTbYh4CCtUQh_tsArRT7cpfyu42WPr5snjNli3H_ph73xOw2qwxeMQb0ITppDiY_Sgs0PxT47nOfr67u2Xqw_V9af3H6_eXFdOSDZVsvGWMUlbKiyz1HWdbDVYQtqWNoxrKpWmra1BagDHpPMATBDuRaO90JKdo9eH3HFudr51Pk7ZDmbMYWfz3iQbzN9KDDemTz8MrwFUDUvAq2NATt9nXyazC8X5YbDRp7kYUKxmy-5B_h-tBRdUMEYX9OU_6DbNednmL0oTqpha3748UC6nUrLvTnMDMWvfZu3b_Ol7cby4-90T_7vgBXh2BFbnKQ6YgQVa5OcHeVumlO_Yuayp4uwnmtq63g</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1759028381</pqid></control><display><type>article</type><title>Rapid and profound rewiring of brain lipid signaling networks by acute diacylglycerol lipase inhibition</title><source>MEDLINE</source><source>Jstor Complete Legacy</source><source>PubMed Central</source><source>Alma/SFX Local Collection</source><source>Free Full-Text Journals in Chemistry</source><creator>Ogasawara, Daisuke ; Deng, Hui ; Viader, Andreu ; Baggelaar, Marc P. ; Breman, Arjen ; den Dulk, Hans ; van den Nieuwendijk, Adrianus M. C. H. ; Soethoudt, Marjolein ; van der Wel, Tom ; Zhou, Juan ; Overkleeft, Herman S. ; Sanchez-Alavez, Manuel ; Mori, Simone ; Nguyen, William ; Conti, Bruno ; Liu, Xiaojie ; Chen, Yao ; Liu, Qing-song ; Cravatt, Benjamin F. ; van der Stelt, Mario</creator><creatorcontrib>Ogasawara, Daisuke ; Deng, Hui ; Viader, Andreu ; Baggelaar, Marc P. ; Breman, Arjen ; den Dulk, Hans ; van den Nieuwendijk, Adrianus M. C. H. ; Soethoudt, Marjolein ; van der Wel, Tom ; Zhou, Juan ; Overkleeft, Herman S. ; Sanchez-Alavez, Manuel ; Mori, Simone ; Nguyen, William ; Conti, Bruno ; Liu, Xiaojie ; Chen, Yao ; Liu, Qing-song ; Cravatt, Benjamin F. ; van der Stelt, Mario</creatorcontrib><description>Diacylglycerol lipases (DAGLα and DAGLβ) convert diacylglycerol to the endocannabinoid 2-arachidonoylglycerol. Our understanding of DAGL function has been hindered by a lack of chemical probes that can perturb these enzymes in vivo. Here, we report a set of centrally active DAGL inhibitors and a structurally related control probe and their use, in combination with chemical proteomics and lipidomics, to determine the impact of acute DAGL blockade on brain lipid networks in mice. Within 2 h, DAGL inhibition produced a striking reorganization of bioactive lipids, including elevations in DAGs and reductions in endocannabinoids and eicosanoids. We also found that DAGLα is a short half-life protein, and the inactivation of DAGLs disrupts cannabinoid receptor-dependent synaptic plasticity and impairs neuroinflammatory responses, including lipopolysaccharide-induced anapyrexia. These findings illuminate the highly interconnected and dynamic nature of lipid signaling pathways in the brain and the central role that DAGL enzymes play in regulating this network.</description><identifier>ISSN: 0027-8424</identifier><identifier>EISSN: 1091-6490</identifier><identifier>DOI: 10.1073/pnas.1522364112</identifier><identifier>PMID: 26668358</identifier><language>eng</language><publisher>United States: National Academy of Sciences</publisher><subject>Animals ; Arachidonic Acids - metabolism ; Biological Sciences ; Brain ; Brain - drug effects ; Brain - enzymology ; Brain - metabolism ; Diglycerides - metabolism ; Endocannabinoids - metabolism ; Enzyme Inhibitors - chemistry ; Enzyme Inhibitors - pharmacology ; Enzymes ; Glycerides - metabolism ; INAUGURAL ARTICLE ; Lipids ; Lipoprotein Lipase - antagonists & inhibitors ; Lipoprotein Lipase - metabolism ; Male ; Mice ; Mice, Inbred C57BL ; Neuronal Plasticity - drug effects ; Proteomics ; Receptors, Cannabinoid - metabolism ; Rodents ; Signal Transduction - drug effects</subject><ispartof>Proceedings of the National Academy of Sciences - PNAS, 2016-01, Vol.113 (1), p.26-33</ispartof><rights>Volumes 1–89 and 106–113, copyright as a collective work only; author(s) retains copyright to individual articles</rights><rights>Copyright National Academy of Sciences Jan 5, 2016</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c563t-6bea3362d25a3a2cff6d91a00dd2b34926892da716911c36ce113504e5b9e5963</citedby><cites>FETCH-LOGICAL-c563t-6bea3362d25a3a2cff6d91a00dd2b34926892da716911c36ce113504e5b9e5963</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Uhttp://www.pnas.org/content/113/1.cover.gif</thumbnail><linktopdf>$$Uhttps://www.jstor.org/stable/pdf/26467284$$EPDF$$P50$$Gjstor$$H</linktopdf><linktohtml>$$Uhttps://www.jstor.org/stable/26467284$$EHTML$$P50$$Gjstor$$H</linktohtml><link.rule.ids>230,314,723,776,780,799,881,27903,27904,53769,53771,57995,58228</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/26668358$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Ogasawara, Daisuke</creatorcontrib><creatorcontrib>Deng, Hui</creatorcontrib><creatorcontrib>Viader, Andreu</creatorcontrib><creatorcontrib>Baggelaar, Marc P.</creatorcontrib><creatorcontrib>Breman, Arjen</creatorcontrib><creatorcontrib>den Dulk, Hans</creatorcontrib><creatorcontrib>van den Nieuwendijk, Adrianus M. C. H.</creatorcontrib><creatorcontrib>Soethoudt, Marjolein</creatorcontrib><creatorcontrib>van der Wel, Tom</creatorcontrib><creatorcontrib>Zhou, Juan</creatorcontrib><creatorcontrib>Overkleeft, Herman S.</creatorcontrib><creatorcontrib>Sanchez-Alavez, Manuel</creatorcontrib><creatorcontrib>Mori, Simone</creatorcontrib><creatorcontrib>Nguyen, William</creatorcontrib><creatorcontrib>Conti, Bruno</creatorcontrib><creatorcontrib>Liu, Xiaojie</creatorcontrib><creatorcontrib>Chen, Yao</creatorcontrib><creatorcontrib>Liu, Qing-song</creatorcontrib><creatorcontrib>Cravatt, Benjamin F.</creatorcontrib><creatorcontrib>van der Stelt, Mario</creatorcontrib><title>Rapid and profound rewiring of brain lipid signaling networks by acute diacylglycerol lipase inhibition</title><title>Proceedings of the National Academy of Sciences - PNAS</title><addtitle>Proc Natl Acad Sci U S A</addtitle><description>Diacylglycerol lipases (DAGLα and DAGLβ) convert diacylglycerol to the endocannabinoid 2-arachidonoylglycerol. Our understanding of DAGL function has been hindered by a lack of chemical probes that can perturb these enzymes in vivo. Here, we report a set of centrally active DAGL inhibitors and a structurally related control probe and their use, in combination with chemical proteomics and lipidomics, to determine the impact of acute DAGL blockade on brain lipid networks in mice. Within 2 h, DAGL inhibition produced a striking reorganization of bioactive lipids, including elevations in DAGs and reductions in endocannabinoids and eicosanoids. We also found that DAGLα is a short half-life protein, and the inactivation of DAGLs disrupts cannabinoid receptor-dependent synaptic plasticity and impairs neuroinflammatory responses, including lipopolysaccharide-induced anapyrexia. These findings illuminate the highly interconnected and dynamic nature of lipid signaling pathways in the brain and the central role that DAGL enzymes play in regulating this network.</description><subject>Animals</subject><subject>Arachidonic Acids - metabolism</subject><subject>Biological Sciences</subject><subject>Brain</subject><subject>Brain - drug effects</subject><subject>Brain - enzymology</subject><subject>Brain - metabolism</subject><subject>Diglycerides - metabolism</subject><subject>Endocannabinoids - metabolism</subject><subject>Enzyme Inhibitors - chemistry</subject><subject>Enzyme Inhibitors - pharmacology</subject><subject>Enzymes</subject><subject>Glycerides - metabolism</subject><subject>INAUGURAL ARTICLE</subject><subject>Lipids</subject><subject>Lipoprotein Lipase - antagonists & inhibitors</subject><subject>Lipoprotein Lipase - metabolism</subject><subject>Male</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Neuronal Plasticity - drug effects</subject><subject>Proteomics</subject><subject>Receptors, Cannabinoid - metabolism</subject><subject>Rodents</subject><subject>Signal Transduction - drug effects</subject><issn>0027-8424</issn><issn>1091-6490</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2016</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkc2L1TAUxYMoznN07UYl4MZNZ3Lz1WQjyOAXDAii65CmaSfPvqQmrcP77219z-foxlUC53dObu5B6CmQCyA1uxyjLRcgKGWSA9B7aANEQyW5JvfRhhBaV4pTfoYelbIlhGihyEN0RqWUigm1Qf1nO4YW29jiMacuzcsl-9uQQ-xx6nCTbYh4CCtUQh_tsArRT7cpfyu42WPr5snjNli3H_ph73xOw2qwxeMQb0ITppDiY_Sgs0PxT47nOfr67u2Xqw_V9af3H6_eXFdOSDZVsvGWMUlbKiyz1HWdbDVYQtqWNoxrKpWmra1BagDHpPMATBDuRaO90JKdo9eH3HFudr51Pk7ZDmbMYWfz3iQbzN9KDDemTz8MrwFUDUvAq2NATt9nXyazC8X5YbDRp7kYUKxmy-5B_h-tBRdUMEYX9OU_6DbNednmL0oTqpha3748UC6nUrLvTnMDMWvfZu3b_Ol7cby4-90T_7vgBXh2BFbnKQ6YgQVa5OcHeVumlO_Yuayp4uwnmtq63g</recordid><startdate>20160105</startdate><enddate>20160105</enddate><creator>Ogasawara, Daisuke</creator><creator>Deng, Hui</creator><creator>Viader, Andreu</creator><creator>Baggelaar, Marc P.</creator><creator>Breman, Arjen</creator><creator>den Dulk, Hans</creator><creator>van den Nieuwendijk, Adrianus M. C. H.</creator><creator>Soethoudt, Marjolein</creator><creator>van der Wel, Tom</creator><creator>Zhou, Juan</creator><creator>Overkleeft, Herman S.</creator><creator>Sanchez-Alavez, Manuel</creator><creator>Mori, Simone</creator><creator>Nguyen, William</creator><creator>Conti, Bruno</creator><creator>Liu, Xiaojie</creator><creator>Chen, Yao</creator><creator>Liu, Qing-song</creator><creator>Cravatt, Benjamin F.</creator><creator>van der Stelt, Mario</creator><general>National Academy of Sciences</general><general>National Acad Sciences</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>7QG</scope><scope>7QL</scope><scope>7QP</scope><scope>7QR</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TK</scope><scope>7TM</scope><scope>7TO</scope><scope>7U9</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>H94</scope><scope>M7N</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20160105</creationdate><title>Rapid and profound rewiring of brain lipid signaling networks by acute diacylglycerol lipase inhibition</title><author>Ogasawara, Daisuke ; Deng, Hui ; Viader, Andreu ; Baggelaar, Marc P. ; Breman, Arjen ; den Dulk, Hans ; van den Nieuwendijk, Adrianus M. C. H. ; Soethoudt, Marjolein ; van der Wel, Tom ; Zhou, Juan ; Overkleeft, Herman S. ; Sanchez-Alavez, Manuel ; Mori, Simone ; Nguyen, William ; Conti, Bruno ; Liu, Xiaojie ; Chen, Yao ; Liu, Qing-song ; Cravatt, Benjamin F. ; van der Stelt, Mario</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c563t-6bea3362d25a3a2cff6d91a00dd2b34926892da716911c36ce113504e5b9e5963</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2016</creationdate><topic>Animals</topic><topic>Arachidonic Acids - metabolism</topic><topic>Biological Sciences</topic><topic>Brain</topic><topic>Brain - drug effects</topic><topic>Brain - enzymology</topic><topic>Brain - metabolism</topic><topic>Diglycerides - metabolism</topic><topic>Endocannabinoids - metabolism</topic><topic>Enzyme Inhibitors - chemistry</topic><topic>Enzyme Inhibitors - pharmacology</topic><topic>Enzymes</topic><topic>Glycerides - metabolism</topic><topic>INAUGURAL ARTICLE</topic><topic>Lipids</topic><topic>Lipoprotein Lipase - antagonists & inhibitors</topic><topic>Lipoprotein Lipase - metabolism</topic><topic>Male</topic><topic>Mice</topic><topic>Mice, Inbred C57BL</topic><topic>Neuronal Plasticity - drug effects</topic><topic>Proteomics</topic><topic>Receptors, Cannabinoid - metabolism</topic><topic>Rodents</topic><topic>Signal Transduction - drug effects</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Ogasawara, Daisuke</creatorcontrib><creatorcontrib>Deng, Hui</creatorcontrib><creatorcontrib>Viader, Andreu</creatorcontrib><creatorcontrib>Baggelaar, Marc P.</creatorcontrib><creatorcontrib>Breman, Arjen</creatorcontrib><creatorcontrib>den Dulk, Hans</creatorcontrib><creatorcontrib>van den Nieuwendijk, Adrianus M. C. H.</creatorcontrib><creatorcontrib>Soethoudt, Marjolein</creatorcontrib><creatorcontrib>van der Wel, Tom</creatorcontrib><creatorcontrib>Zhou, Juan</creatorcontrib><creatorcontrib>Overkleeft, Herman S.</creatorcontrib><creatorcontrib>Sanchez-Alavez, Manuel</creatorcontrib><creatorcontrib>Mori, Simone</creatorcontrib><creatorcontrib>Nguyen, William</creatorcontrib><creatorcontrib>Conti, Bruno</creatorcontrib><creatorcontrib>Liu, Xiaojie</creatorcontrib><creatorcontrib>Chen, Yao</creatorcontrib><creatorcontrib>Liu, Qing-song</creatorcontrib><creatorcontrib>Cravatt, Benjamin F.</creatorcontrib><creatorcontrib>van der Stelt, Mario</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Animal Behavior Abstracts</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Chemoreception Abstracts</collection><collection>Ecology Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Immunology Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Proceedings of the National Academy of Sciences - PNAS</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Ogasawara, Daisuke</au><au>Deng, Hui</au><au>Viader, Andreu</au><au>Baggelaar, Marc P.</au><au>Breman, Arjen</au><au>den Dulk, Hans</au><au>van den Nieuwendijk, Adrianus M. C. H.</au><au>Soethoudt, Marjolein</au><au>van der Wel, Tom</au><au>Zhou, Juan</au><au>Overkleeft, Herman S.</au><au>Sanchez-Alavez, Manuel</au><au>Mori, Simone</au><au>Nguyen, William</au><au>Conti, Bruno</au><au>Liu, Xiaojie</au><au>Chen, Yao</au><au>Liu, Qing-song</au><au>Cravatt, Benjamin F.</au><au>van der Stelt, Mario</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Rapid and profound rewiring of brain lipid signaling networks by acute diacylglycerol lipase inhibition</atitle><jtitle>Proceedings of the National Academy of Sciences - PNAS</jtitle><addtitle>Proc Natl Acad Sci U S A</addtitle><date>2016-01-05</date><risdate>2016</risdate><volume>113</volume><issue>1</issue><spage>26</spage><epage>33</epage><pages>26-33</pages><issn>0027-8424</issn><eissn>1091-6490</eissn><abstract>Diacylglycerol lipases (DAGLα and DAGLβ) convert diacylglycerol to the endocannabinoid 2-arachidonoylglycerol. Our understanding of DAGL function has been hindered by a lack of chemical probes that can perturb these enzymes in vivo. Here, we report a set of centrally active DAGL inhibitors and a structurally related control probe and their use, in combination with chemical proteomics and lipidomics, to determine the impact of acute DAGL blockade on brain lipid networks in mice. Within 2 h, DAGL inhibition produced a striking reorganization of bioactive lipids, including elevations in DAGs and reductions in endocannabinoids and eicosanoids. We also found that DAGLα is a short half-life protein, and the inactivation of DAGLs disrupts cannabinoid receptor-dependent synaptic plasticity and impairs neuroinflammatory responses, including lipopolysaccharide-induced anapyrexia. These findings illuminate the highly interconnected and dynamic nature of lipid signaling pathways in the brain and the central role that DAGL enzymes play in regulating this network.</abstract><cop>United States</cop><pub>National Academy of Sciences</pub><pmid>26668358</pmid><doi>10.1073/pnas.1522364112</doi><tpages>8</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0027-8424 |
| ispartof | Proceedings of the National Academy of Sciences - PNAS, 2016-01, Vol.113 (1), p.26-33 |
| issn | 0027-8424 1091-6490 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_1837310716 |
| source | MEDLINE; Jstor Complete Legacy; PubMed Central; Alma/SFX Local Collection; Free Full-Text Journals in Chemistry |
| subjects | Animals Arachidonic Acids - metabolism Biological Sciences Brain Brain - drug effects Brain - enzymology Brain - metabolism Diglycerides - metabolism Endocannabinoids - metabolism Enzyme Inhibitors - chemistry Enzyme Inhibitors - pharmacology Enzymes Glycerides - metabolism INAUGURAL ARTICLE Lipids Lipoprotein Lipase - antagonists & inhibitors Lipoprotein Lipase - metabolism Male Mice Mice, Inbred C57BL Neuronal Plasticity - drug effects Proteomics Receptors, Cannabinoid - metabolism Rodents Signal Transduction - drug effects |
| title | Rapid and profound rewiring of brain lipid signaling networks by acute diacylglycerol lipase inhibition |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-24T00%3A26%3A27IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-jstor_proqu&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Rapid%20and%20profound%20rewiring%20of%20brain%20lipid%20signaling%20networks%20by%20acute%20diacylglycerol%20lipase%20inhibition&rft.jtitle=Proceedings%20of%20the%20National%20Academy%20of%20Sciences%20-%20PNAS&rft.au=Ogasawara,%20Daisuke&rft.date=2016-01-05&rft.volume=113&rft.issue=1&rft.spage=26&rft.epage=33&rft.pages=26-33&rft.issn=0027-8424&rft.eissn=1091-6490&rft_id=info:doi/10.1073/pnas.1522364112&rft_dat=%3Cjstor_proqu%3E26467284%3C/jstor_proqu%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1759028381&rft_id=info:pmid/26668358&rft_jstor_id=26467284&rfr_iscdi=true |