Effects of matrix metalloproteinase inhibitors on N-methyl-D-aspartate receptor and contribute to long-term potentiation in the anterior cingulate cortex of adult mice
Matrix metalloproteinases (MMPs) have been suggested to contribute to long-term potentiation, behavioral learning, and memory. In the dorsal horn of spinal cord, MMPs were reported to contribute to injury-related changes, and inhibitors of MMPs have been proposed as potential analgesics. However, it...
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| Veröffentlicht in: | Molecular pain 2019-01, Vol.15, p.1744806919842958-1744806919842958 |
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| description | Matrix metalloproteinases (MMPs) have been suggested to contribute to long-term potentiation, behavioral learning, and memory. In the dorsal horn of spinal cord, MMPs were reported to contribute to injury-related changes, and inhibitors of MMPs have been proposed as potential analgesics. However, it is unclear whether MMP inhibitors produce these effects by inhibiting the function of N-methyl-D-aspartate receptor (NMDAR), a key receptor for the induction of long-term potentiation. In this study, we wanted to examine if MMP inhibitors affect NMDAR-mediated excitatory postsynaptic currents in the anterior cingulate cortex of adult mice. Among different subtype inhibitors we used, we found that MMP-9 and MMP-2/9 inhibitors did not change NMDAR-mediated excitatory postsynaptic currents. However, MMP-3 and broad-spectrum MMP inhibitors reduced the NMDAR-mediated excitatory postsynaptic currents. Consistently, MMP-9 and MMP-2/9 inhibitors had no effect on NMDAR-dependent long-term potentiation, but MMP-3 and broad-spectrum MMP inhibitors inhibited the induction of long-term potentiation. Our results suggest that MMP inhibitors may produce their effects by inhibiting NMDAR functions in central synapses. |
| doi_str_mv | 10.1177/1744806919842958 |
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In the dorsal horn of spinal cord, MMPs were reported to contribute to injury-related changes, and inhibitors of MMPs have been proposed as potential analgesics. However, it is unclear whether MMP inhibitors produce these effects by inhibiting the function of N-methyl-D-aspartate receptor (NMDAR), a key receptor for the induction of long-term potentiation. In this study, we wanted to examine if MMP inhibitors affect NMDAR-mediated excitatory postsynaptic currents in the anterior cingulate cortex of adult mice. Among different subtype inhibitors we used, we found that MMP-9 and MMP-2/9 inhibitors did not change NMDAR-mediated excitatory postsynaptic currents. However, MMP-3 and broad-spectrum MMP inhibitors reduced the NMDAR-mediated excitatory postsynaptic currents. Consistently, MMP-9 and MMP-2/9 inhibitors had no effect on NMDAR-dependent long-term potentiation, but MMP-3 and broad-spectrum MMP inhibitors inhibited the induction of long-term potentiation. Our results suggest that MMP inhibitors may produce their effects by inhibiting NMDAR functions in central synapses.</description><identifier>ISSN: 1744-8069</identifier><identifier>EISSN: 1744-8069</identifier><identifier>DOI: 10.1177/1744806919842958</identifier><identifier>PMID: 30900509</identifier><language>eng</language><publisher>Los Angeles, CA: SAGE Publications</publisher><subject>Analgesics ; Animals ; Cortex (cingulate) ; Dorsal horn ; Excitatory postsynaptic potentials ; Gelatinase A ; Gelatinase B ; Glutamic acid receptors ; Gyrus Cinguli - drug effects ; Gyrus Cinguli - metabolism ; Long-term potentiation ; Long-Term Potentiation - drug effects ; Long-Term Potentiation - physiology ; Male ; Matrix metalloproteinase ; Matrix Metalloproteinase 2 - metabolism ; Matrix Metalloproteinase 3 - metabolism ; Matrix Metalloproteinase 9 - metabolism ; Matrix Metalloproteinase Inhibitors - pharmacology ; Metalloproteinase ; Mice ; Mice, Inbred C57BL ; N-Methyl-D-aspartic acid receptors ; Receptors, N-Methyl-D-Aspartate - antagonists & inhibitors ; Receptors, N-Methyl-D-Aspartate - metabolism ; Spinal cord injuries ; Stromelysin 1</subject><ispartof>Molecular pain, 2019-01, Vol.15, p.1744806919842958-1744806919842958</ispartof><rights>The Author(s) 2019</rights><rights>The Author(s) 2019. This work is licensed under the Creative Commons Attribution – Non-Commercial License http://creativecommons.org/licenses/by-nc/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>The Author(s) 2019 2019 SAGE Publications Inc., unless otherwise noted. Manuscript content on this site is licensed under Creative Commons Licenses</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c528t-becceb430c89eff8a9fb38da64cad28dd0b7462b7b414e16c0458fb4729f35c53</citedby><cites>FETCH-LOGICAL-c528t-becceb430c89eff8a9fb38da64cad28dd0b7462b7b414e16c0458fb4729f35c53</cites><orcidid>0000-0003-1956-0553 ; 0000-0001-9062-3241</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6480992/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6480992/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,881,21945,27830,27901,27902,44921,45309,53766,53768</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/30900509$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Matsuura, Takanori</creatorcontrib><creatorcontrib>Li, Xu-Hui</creatorcontrib><creatorcontrib>Tao, Chen</creatorcontrib><creatorcontrib>Zhuo, Min</creatorcontrib><title>Effects of matrix metalloproteinase inhibitors on N-methyl-D-aspartate receptor and contribute to long-term potentiation in the anterior cingulate cortex of adult mice</title><title>Molecular pain</title><addtitle>Mol Pain</addtitle><description>Matrix metalloproteinases (MMPs) have been suggested to contribute to long-term potentiation, behavioral learning, and memory. In the dorsal horn of spinal cord, MMPs were reported to contribute to injury-related changes, and inhibitors of MMPs have been proposed as potential analgesics. However, it is unclear whether MMP inhibitors produce these effects by inhibiting the function of N-methyl-D-aspartate receptor (NMDAR), a key receptor for the induction of long-term potentiation. In this study, we wanted to examine if MMP inhibitors affect NMDAR-mediated excitatory postsynaptic currents in the anterior cingulate cortex of adult mice. Among different subtype inhibitors we used, we found that MMP-9 and MMP-2/9 inhibitors did not change NMDAR-mediated excitatory postsynaptic currents. However, MMP-3 and broad-spectrum MMP inhibitors reduced the NMDAR-mediated excitatory postsynaptic currents. Consistently, MMP-9 and MMP-2/9 inhibitors had no effect on NMDAR-dependent long-term potentiation, but MMP-3 and broad-spectrum MMP inhibitors inhibited the induction of long-term potentiation. Our results suggest that MMP inhibitors may produce their effects by inhibiting NMDAR functions in central synapses.</description><subject>Analgesics</subject><subject>Animals</subject><subject>Cortex (cingulate)</subject><subject>Dorsal horn</subject><subject>Excitatory postsynaptic potentials</subject><subject>Gelatinase A</subject><subject>Gelatinase B</subject><subject>Glutamic acid receptors</subject><subject>Gyrus Cinguli - drug effects</subject><subject>Gyrus Cinguli - metabolism</subject><subject>Long-term potentiation</subject><subject>Long-Term Potentiation - drug effects</subject><subject>Long-Term Potentiation - physiology</subject><subject>Male</subject><subject>Matrix metalloproteinase</subject><subject>Matrix Metalloproteinase 2 - metabolism</subject><subject>Matrix Metalloproteinase 3 - metabolism</subject><subject>Matrix Metalloproteinase 9 - metabolism</subject><subject>Matrix Metalloproteinase Inhibitors - pharmacology</subject><subject>Metalloproteinase</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>N-Methyl-D-aspartic acid receptors</subject><subject>Receptors, N-Methyl-D-Aspartate - antagonists & inhibitors</subject><subject>Receptors, N-Methyl-D-Aspartate - metabolism</subject><subject>Spinal cord injuries</subject><subject>Stromelysin 1</subject><issn>1744-8069</issn><issn>1744-8069</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><sourceid>AFRWT</sourceid><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNp1kkFvFSEQgDdGY2v17smQePFChV12Fy4mplZr0uhFzwTY4T0aFlZgTfuL_JuyebXWJp4gM998zGRompeUnFI6jm_pyBgng6CCs1b0_FFzvIXwFnt8737UPMv5ipBuJAN92hx1RBDSE3Hc_Dq3FkzJKFo0q5LcNZqhKO_jkmIBF1QG5MLeaVdiqlhAX3Al9jcef8AqLyoVVQAlMLBUAqkwIRNDNem1xktEPoYdLpBmtFRjKE4VVzUuoLKHyteUq4XGhd3qN5eJqcD11pGaVl_Q7Aw8b55Y5TO8uD1Pmu8fz7-dXeDLr58-n72_xKZvecEajAHNOmK4AGu5ElZ3fFIDM2pq-TQRPbKh1aNmlAEdDGE9t5qNrbBdb_rupHl38C6rnmEytd-kvFySm1W6kVE5-W8muL3cxZ9yqIsQoq2CN7eCFH-skIucXTbgvQoQ1yxbKoa-FWRgFX39AL2Kawp1PNkyVhfKRU8qRQ6USTHnBPauGUrk9gvkw19QS17dH-Ku4M_aK4APQFY7-Pvqf4W_AVcev70</recordid><startdate>201901</startdate><enddate>201901</enddate><creator>Matsuura, Takanori</creator><creator>Li, Xu-Hui</creator><creator>Tao, Chen</creator><creator>Zhuo, Min</creator><general>SAGE Publications</general><general>Sage Publications Ltd</general><scope>AFRWT</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>7TK</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>K9.</scope><scope>M0S</scope><scope>M1P</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0003-1956-0553</orcidid><orcidid>https://orcid.org/0000-0001-9062-3241</orcidid></search><sort><creationdate>201901</creationdate><title>Effects of matrix metalloproteinase inhibitors on N-methyl-D-aspartate receptor and contribute to long-term potentiation in the anterior cingulate cortex of adult mice</title><author>Matsuura, Takanori ; Li, Xu-Hui ; Tao, Chen ; Zhuo, Min</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c528t-becceb430c89eff8a9fb38da64cad28dd0b7462b7b414e16c0458fb4729f35c53</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><topic>Analgesics</topic><topic>Animals</topic><topic>Cortex (cingulate)</topic><topic>Dorsal horn</topic><topic>Excitatory postsynaptic potentials</topic><topic>Gelatinase A</topic><topic>Gelatinase B</topic><topic>Glutamic acid receptors</topic><topic>Gyrus Cinguli - drug effects</topic><topic>Gyrus Cinguli - metabolism</topic><topic>Long-term potentiation</topic><topic>Long-Term Potentiation - drug effects</topic><topic>Long-Term Potentiation - physiology</topic><topic>Male</topic><topic>Matrix metalloproteinase</topic><topic>Matrix Metalloproteinase 2 - metabolism</topic><topic>Matrix Metalloproteinase 3 - metabolism</topic><topic>Matrix Metalloproteinase 9 - metabolism</topic><topic>Matrix Metalloproteinase Inhibitors - pharmacology</topic><topic>Metalloproteinase</topic><topic>Mice</topic><topic>Mice, Inbred C57BL</topic><topic>N-Methyl-D-aspartic acid receptors</topic><topic>Receptors, N-Methyl-D-Aspartate - antagonists & inhibitors</topic><topic>Receptors, N-Methyl-D-Aspartate - metabolism</topic><topic>Spinal cord injuries</topic><topic>Stromelysin 1</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Matsuura, Takanori</creatorcontrib><creatorcontrib>Li, Xu-Hui</creatorcontrib><creatorcontrib>Tao, Chen</creatorcontrib><creatorcontrib>Zhuo, Min</creatorcontrib><collection>Sage Journals GOLD Open Access 2024</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>Neurosciences Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</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>ProQuest Central</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 Health & Medical Complete (Alumni)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Publicly Available Content 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>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Molecular pain</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Matsuura, Takanori</au><au>Li, Xu-Hui</au><au>Tao, Chen</au><au>Zhuo, Min</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Effects of matrix metalloproteinase inhibitors on N-methyl-D-aspartate receptor and contribute to long-term potentiation in the anterior cingulate cortex of adult mice</atitle><jtitle>Molecular pain</jtitle><addtitle>Mol Pain</addtitle><date>2019-01</date><risdate>2019</risdate><volume>15</volume><spage>1744806919842958</spage><epage>1744806919842958</epage><pages>1744806919842958-1744806919842958</pages><issn>1744-8069</issn><eissn>1744-8069</eissn><abstract>Matrix metalloproteinases (MMPs) have been suggested to contribute to long-term potentiation, behavioral learning, and memory. In the dorsal horn of spinal cord, MMPs were reported to contribute to injury-related changes, and inhibitors of MMPs have been proposed as potential analgesics. However, it is unclear whether MMP inhibitors produce these effects by inhibiting the function of N-methyl-D-aspartate receptor (NMDAR), a key receptor for the induction of long-term potentiation. In this study, we wanted to examine if MMP inhibitors affect NMDAR-mediated excitatory postsynaptic currents in the anterior cingulate cortex of adult mice. Among different subtype inhibitors we used, we found that MMP-9 and MMP-2/9 inhibitors did not change NMDAR-mediated excitatory postsynaptic currents. However, MMP-3 and broad-spectrum MMP inhibitors reduced the NMDAR-mediated excitatory postsynaptic currents. Consistently, MMP-9 and MMP-2/9 inhibitors had no effect on NMDAR-dependent long-term potentiation, but MMP-3 and broad-spectrum MMP inhibitors inhibited the induction of long-term potentiation. Our results suggest that MMP inhibitors may produce their effects by inhibiting NMDAR functions in central synapses.</abstract><cop>Los Angeles, CA</cop><pub>SAGE Publications</pub><pmid>30900509</pmid><doi>10.1177/1744806919842958</doi><orcidid>https://orcid.org/0000-0003-1956-0553</orcidid><orcidid>https://orcid.org/0000-0001-9062-3241</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | Analgesics Animals Cortex (cingulate) Dorsal horn Excitatory postsynaptic potentials Gelatinase A Gelatinase B Glutamic acid receptors Gyrus Cinguli - drug effects Gyrus Cinguli - metabolism Long-term potentiation Long-Term Potentiation - drug effects Long-Term Potentiation - physiology Male Matrix metalloproteinase Matrix Metalloproteinase 2 - metabolism Matrix Metalloproteinase 3 - metabolism Matrix Metalloproteinase 9 - metabolism Matrix Metalloproteinase Inhibitors - pharmacology Metalloproteinase Mice Mice, Inbred C57BL N-Methyl-D-aspartic acid receptors Receptors, N-Methyl-D-Aspartate - antagonists & inhibitors Receptors, N-Methyl-D-Aspartate - metabolism Spinal cord injuries Stromelysin 1 |
| title | Effects of matrix metalloproteinase inhibitors on N-methyl-D-aspartate receptor and contribute to long-term potentiation in the anterior cingulate cortex of adult mice |
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