The effect of bilirubin on the excitability of mitral cells in the olfactory bulb of the rat
Olfactory dysfunction is a common clinical phenomenon observed in various liver diseases. Previous studies have shown a correlation between smell disorders and bilirubin levels in patients with hepatic diseases. Bilirubin is a well-known neurotoxin; however, its effect on neurons in the main olfacto...
Gespeichert in:
| Veröffentlicht in: | Scientific reports 2016-09, Vol.6 (1), p.32872, Article 32872 |
|---|---|
| Hauptverfasser: | , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | |
|---|---|
| container_issue | 1 |
| container_start_page | 32872 |
| container_title | Scientific reports |
| container_volume | 6 |
| creator | Chen, Xiao-Juan Zhou, Hui-Qun Ye, Hai-bo Li, Chun-Yan Zhang, Wei-Tian |
| description | Olfactory dysfunction is a common clinical phenomenon observed in various liver diseases. Previous studies have shown a correlation between smell disorders and bilirubin levels in patients with hepatic diseases. Bilirubin is a well-known neurotoxin; however, its effect on neurons in the main olfactory bulb (MOB), the first relay in the olfactory system, has not been examined. We investigated the effect of bilirubin (>3 μM) on mitral cells (MCs), the principal output neurons of the MOB. Bilirubin increased the frequency of spontaneous firing and the frequency but not the amplitude of spontaneous excitatory postsynaptic currents (sEPSCs). TTX completely blocked sEPSCs in almost all of the cells tested. Bilirubin activity was partially blocked by N-methyl-D-aspartate (NMDA) and α-amino-3-hydroxy-5-methyl-4-isoxazolepro pionic acid (AMPA) receptor antagonists. Furthermore, we found that bilirubin increased the frequency of intrinsic firing independent of synaptic transmission in MCs. Our findings suggest that bilirubin enhances glutamatergic transmission and strengthens intrinsic firing independent of synaptic transmission, all of which cause hyperexcitability in MCs. Our findings provide the basis for further investigation into the mechanisms underlying olfactory dysfunction that are often observed in patients with severe liver disease. |
| doi_str_mv | 10.1038/srep32872 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_5017196</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>1899062047</sourcerecordid><originalsourceid>FETCH-LOGICAL-c438t-4fb827cac8efff453a331ced614e163a450f88d725346c9ed8f0fd926a0785b93</originalsourceid><addsrcrecordid>eNplkV1LwzAUhoMobsxd-Aek4JVCNR9Nm9wIMvwCwZt5J4Q0TbaMrplpKu7fm9I5JubmhHMe3vPyHgDOEbxBkLDb1usNwazAR2CMYUZTTDA-PviPwLRtVzA-inmG-CkY4SJHiHI-Bh_zpU60MVqFxJmktLX1XWmbxDVJ6EffygbZt8O2B9Y2eFknStd1m9iBcbWRKji_TcquLnuq73oZzsCJkXWrp7s6Ae-PD_PZc_r69vQyu39NVUZYSDNTMlwoqVg0YjJKJCFI6SpHmUY5kRmFhrGqwJRkueK6YgaaiuNcwoLRkpMJuBt0N1251pXSTW9SbLxdS78VTlrxd9LYpVi4L0EhKhDPo8DlTsC7z063Qaxc55voWSDGOcxjmEWkrgZKedfG2M1-A4Kiv4XY3yKyF4eW9uRv8hG4HoA2jpqF9gcr_6n9AOWxlAY</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1899062047</pqid></control><display><type>article</type><title>The effect of bilirubin on the excitability of mitral cells in the olfactory bulb of the rat</title><source>Nature Free</source><source>DOAJ Directory of Open Access Journals</source><source>EZB-FREE-00999 freely available EZB journals</source><source>PubMed Central</source><source>Alma/SFX Local Collection</source><source>Free Full-Text Journals in Chemistry</source><source>Springer Nature OA Free Journals</source><creator>Chen, Xiao-Juan ; Zhou, Hui-Qun ; Ye, Hai-bo ; Li, Chun-Yan ; Zhang, Wei-Tian</creator><creatorcontrib>Chen, Xiao-Juan ; Zhou, Hui-Qun ; Ye, Hai-bo ; Li, Chun-Yan ; Zhang, Wei-Tian</creatorcontrib><description>Olfactory dysfunction is a common clinical phenomenon observed in various liver diseases. Previous studies have shown a correlation between smell disorders and bilirubin levels in patients with hepatic diseases. Bilirubin is a well-known neurotoxin; however, its effect on neurons in the main olfactory bulb (MOB), the first relay in the olfactory system, has not been examined. We investigated the effect of bilirubin (>3 μM) on mitral cells (MCs), the principal output neurons of the MOB. Bilirubin increased the frequency of spontaneous firing and the frequency but not the amplitude of spontaneous excitatory postsynaptic currents (sEPSCs). TTX completely blocked sEPSCs in almost all of the cells tested. Bilirubin activity was partially blocked by N-methyl-D-aspartate (NMDA) and α-amino-3-hydroxy-5-methyl-4-isoxazolepro pionic acid (AMPA) receptor antagonists. Furthermore, we found that bilirubin increased the frequency of intrinsic firing independent of synaptic transmission in MCs. Our findings suggest that bilirubin enhances glutamatergic transmission and strengthens intrinsic firing independent of synaptic transmission, all of which cause hyperexcitability in MCs. Our findings provide the basis for further investigation into the mechanisms underlying olfactory dysfunction that are often observed in patients with severe liver disease.</description><identifier>ISSN: 2045-2322</identifier><identifier>EISSN: 2045-2322</identifier><identifier>DOI: 10.1038/srep32872</identifier><identifier>PMID: 27611599</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>631/378/2624 ; 692/699/375 ; Bilirubin ; Excitability ; Excitatory postsynaptic potentials ; Firing rate ; Glutamatergic transmission ; Glutamic acid receptors ; Humanities and Social Sciences ; Liver diseases ; Mitral cells ; multidisciplinary ; Olfaction ; Olfactory bulb ; Olfactory system ; Rodents ; Science ; Smell ; Synaptic transmission ; Tetrodotoxin ; α-Amino-3-hydroxy-5-methyl-4-isoxazole propionic acid</subject><ispartof>Scientific reports, 2016-09, Vol.6 (1), p.32872, Article 32872</ispartof><rights>The Author(s) 2016</rights><rights>Copyright Nature Publishing Group Sep 2016</rights><rights>Copyright © 2016, The Author(s) 2016 The Author(s)</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c438t-4fb827cac8efff453a331ced614e163a450f88d725346c9ed8f0fd926a0785b93</citedby><cites>FETCH-LOGICAL-c438t-4fb827cac8efff453a331ced614e163a450f88d725346c9ed8f0fd926a0785b93</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/PMC5017196/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5017196/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,27901,27902,41096,42165,51551,53766,53768</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/27611599$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Chen, Xiao-Juan</creatorcontrib><creatorcontrib>Zhou, Hui-Qun</creatorcontrib><creatorcontrib>Ye, Hai-bo</creatorcontrib><creatorcontrib>Li, Chun-Yan</creatorcontrib><creatorcontrib>Zhang, Wei-Tian</creatorcontrib><title>The effect of bilirubin on the excitability of mitral cells in the olfactory bulb of the rat</title><title>Scientific reports</title><addtitle>Sci Rep</addtitle><addtitle>Sci Rep</addtitle><description>Olfactory dysfunction is a common clinical phenomenon observed in various liver diseases. Previous studies have shown a correlation between smell disorders and bilirubin levels in patients with hepatic diseases. Bilirubin is a well-known neurotoxin; however, its effect on neurons in the main olfactory bulb (MOB), the first relay in the olfactory system, has not been examined. We investigated the effect of bilirubin (>3 μM) on mitral cells (MCs), the principal output neurons of the MOB. Bilirubin increased the frequency of spontaneous firing and the frequency but not the amplitude of spontaneous excitatory postsynaptic currents (sEPSCs). TTX completely blocked sEPSCs in almost all of the cells tested. Bilirubin activity was partially blocked by N-methyl-D-aspartate (NMDA) and α-amino-3-hydroxy-5-methyl-4-isoxazolepro pionic acid (AMPA) receptor antagonists. Furthermore, we found that bilirubin increased the frequency of intrinsic firing independent of synaptic transmission in MCs. Our findings suggest that bilirubin enhances glutamatergic transmission and strengthens intrinsic firing independent of synaptic transmission, all of which cause hyperexcitability in MCs. Our findings provide the basis for further investigation into the mechanisms underlying olfactory dysfunction that are often observed in patients with severe liver disease.</description><subject>631/378/2624</subject><subject>692/699/375</subject><subject>Bilirubin</subject><subject>Excitability</subject><subject>Excitatory postsynaptic potentials</subject><subject>Firing rate</subject><subject>Glutamatergic transmission</subject><subject>Glutamic acid receptors</subject><subject>Humanities and Social Sciences</subject><subject>Liver diseases</subject><subject>Mitral cells</subject><subject>multidisciplinary</subject><subject>Olfaction</subject><subject>Olfactory bulb</subject><subject>Olfactory system</subject><subject>Rodents</subject><subject>Science</subject><subject>Smell</subject><subject>Synaptic transmission</subject><subject>Tetrodotoxin</subject><subject>α-Amino-3-hydroxy-5-methyl-4-isoxazole propionic acid</subject><issn>2045-2322</issn><issn>2045-2322</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2016</creationdate><recordtype>article</recordtype><sourceid>C6C</sourceid><sourceid>BENPR</sourceid><recordid>eNplkV1LwzAUhoMobsxd-Aek4JVCNR9Nm9wIMvwCwZt5J4Q0TbaMrplpKu7fm9I5JubmhHMe3vPyHgDOEbxBkLDb1usNwazAR2CMYUZTTDA-PviPwLRtVzA-inmG-CkY4SJHiHI-Bh_zpU60MVqFxJmktLX1XWmbxDVJ6EffygbZt8O2B9Y2eFknStd1m9iBcbWRKji_TcquLnuq73oZzsCJkXWrp7s6Ae-PD_PZc_r69vQyu39NVUZYSDNTMlwoqVg0YjJKJCFI6SpHmUY5kRmFhrGqwJRkueK6YgaaiuNcwoLRkpMJuBt0N1251pXSTW9SbLxdS78VTlrxd9LYpVi4L0EhKhDPo8DlTsC7z063Qaxc55voWSDGOcxjmEWkrgZKedfG2M1-A4Kiv4XY3yKyF4eW9uRv8hG4HoA2jpqF9gcr_6n9AOWxlAY</recordid><startdate>20160909</startdate><enddate>20160909</enddate><creator>Chen, Xiao-Juan</creator><creator>Zhou, Hui-Qun</creator><creator>Ye, Hai-bo</creator><creator>Li, Chun-Yan</creator><creator>Zhang, Wei-Tian</creator><general>Nature Publishing Group UK</general><general>Nature Publishing Group</general><scope>C6C</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7X7</scope><scope>7XB</scope><scope>88A</scope><scope>88E</scope><scope>88I</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AEUYN</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>M2P</scope><scope>M7P</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>Q9U</scope><scope>5PM</scope></search><sort><creationdate>20160909</creationdate><title>The effect of bilirubin on the excitability of mitral cells in the olfactory bulb of the rat</title><author>Chen, Xiao-Juan ; Zhou, Hui-Qun ; Ye, Hai-bo ; Li, Chun-Yan ; Zhang, Wei-Tian</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c438t-4fb827cac8efff453a331ced614e163a450f88d725346c9ed8f0fd926a0785b93</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2016</creationdate><topic>631/378/2624</topic><topic>692/699/375</topic><topic>Bilirubin</topic><topic>Excitability</topic><topic>Excitatory postsynaptic potentials</topic><topic>Firing rate</topic><topic>Glutamatergic transmission</topic><topic>Glutamic acid receptors</topic><topic>Humanities and Social Sciences</topic><topic>Liver diseases</topic><topic>Mitral cells</topic><topic>multidisciplinary</topic><topic>Olfaction</topic><topic>Olfactory bulb</topic><topic>Olfactory system</topic><topic>Rodents</topic><topic>Science</topic><topic>Smell</topic><topic>Synaptic transmission</topic><topic>Tetrodotoxin</topic><topic>α-Amino-3-hydroxy-5-methyl-4-isoxazole propionic acid</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Chen, Xiao-Juan</creatorcontrib><creatorcontrib>Zhou, Hui-Qun</creatorcontrib><creatorcontrib>Ye, Hai-bo</creatorcontrib><creatorcontrib>Li, Chun-Yan</creatorcontrib><creatorcontrib>Zhang, Wei-Tian</creatorcontrib><collection>Springer Nature OA Free Journals</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Biology Database (Alumni Edition)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Science Database (Alumni Edition)</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 One Sustainability</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>Science Database</collection><collection>Biological Science 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>ProQuest Central Basic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Scientific reports</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Chen, Xiao-Juan</au><au>Zhou, Hui-Qun</au><au>Ye, Hai-bo</au><au>Li, Chun-Yan</au><au>Zhang, Wei-Tian</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The effect of bilirubin on the excitability of mitral cells in the olfactory bulb of the rat</atitle><jtitle>Scientific reports</jtitle><stitle>Sci Rep</stitle><addtitle>Sci Rep</addtitle><date>2016-09-09</date><risdate>2016</risdate><volume>6</volume><issue>1</issue><spage>32872</spage><pages>32872-</pages><artnum>32872</artnum><issn>2045-2322</issn><eissn>2045-2322</eissn><abstract>Olfactory dysfunction is a common clinical phenomenon observed in various liver diseases. Previous studies have shown a correlation between smell disorders and bilirubin levels in patients with hepatic diseases. Bilirubin is a well-known neurotoxin; however, its effect on neurons in the main olfactory bulb (MOB), the first relay in the olfactory system, has not been examined. We investigated the effect of bilirubin (>3 μM) on mitral cells (MCs), the principal output neurons of the MOB. Bilirubin increased the frequency of spontaneous firing and the frequency but not the amplitude of spontaneous excitatory postsynaptic currents (sEPSCs). TTX completely blocked sEPSCs in almost all of the cells tested. Bilirubin activity was partially blocked by N-methyl-D-aspartate (NMDA) and α-amino-3-hydroxy-5-methyl-4-isoxazolepro pionic acid (AMPA) receptor antagonists. Furthermore, we found that bilirubin increased the frequency of intrinsic firing independent of synaptic transmission in MCs. Our findings suggest that bilirubin enhances glutamatergic transmission and strengthens intrinsic firing independent of synaptic transmission, all of which cause hyperexcitability in MCs. Our findings provide the basis for further investigation into the mechanisms underlying olfactory dysfunction that are often observed in patients with severe liver disease.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>27611599</pmid><doi>10.1038/srep32872</doi><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 2045-2322 |
| ispartof | Scientific reports, 2016-09, Vol.6 (1), p.32872, Article 32872 |
| issn | 2045-2322 2045-2322 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_5017196 |
| source | Nature Free; DOAJ Directory of Open Access Journals; EZB-FREE-00999 freely available EZB journals; PubMed Central; Alma/SFX Local Collection; Free Full-Text Journals in Chemistry; Springer Nature OA Free Journals |
| subjects | 631/378/2624 692/699/375 Bilirubin Excitability Excitatory postsynaptic potentials Firing rate Glutamatergic transmission Glutamic acid receptors Humanities and Social Sciences Liver diseases Mitral cells multidisciplinary Olfaction Olfactory bulb Olfactory system Rodents Science Smell Synaptic transmission Tetrodotoxin α-Amino-3-hydroxy-5-methyl-4-isoxazole propionic acid |
| title | The effect of bilirubin on the excitability of mitral cells in the olfactory bulb of the rat |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-08T14%3A39%3A43IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=The%20effect%20of%20bilirubin%20on%20the%20excitability%20of%20mitral%20cells%20in%20the%20olfactory%20bulb%20of%20the%20rat&rft.jtitle=Scientific%20reports&rft.au=Chen,%20Xiao-Juan&rft.date=2016-09-09&rft.volume=6&rft.issue=1&rft.spage=32872&rft.pages=32872-&rft.artnum=32872&rft.issn=2045-2322&rft.eissn=2045-2322&rft_id=info:doi/10.1038/srep32872&rft_dat=%3Cproquest_pubme%3E1899062047%3C/proquest_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1899062047&rft_id=info:pmid/27611599&rfr_iscdi=true |