The CD44 ligand hyaluronic acid is elevated in the cerebrospinal fluid of suicide attempters and is associated with increased blood–brain barrier permeability
Abstract Background The glycosaminoglycan hyaluronic acid (HA) is an important component of the extracellular matrix (ECM) in the brain. CD44 is a cell adhesion molecule that binds to HA in the ECM and is present on astrocytes, microglia and certain neurons. Cell adhesion molecules have been reporte...
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| Veröffentlicht in: | Journal of affective disorders 2016-03, Vol.193, p.349-354 |
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| creator | Ventorp, F Barzilay, R Erhardt, S Samuelsson, M Träskman-Bendz, L Janelidze, S Weizman, A Offen, D Brundin, L |
| description | Abstract Background The glycosaminoglycan hyaluronic acid (HA) is an important component of the extracellular matrix (ECM) in the brain. CD44 is a cell adhesion molecule that binds to HA in the ECM and is present on astrocytes, microglia and certain neurons. Cell adhesion molecules have been reported to be involved in anxiety and mood disorders. CD44 levels are decreased in the cerebrospinal fluid (CSF) of depressed individuals, and the CD44 gene has been identified in brain GWAS studies as a possible risk gene for suicidal behavior. Method We measured the CSF levels of HA and the soluble CD44 (sCD44) in suicide attempters ( n =94) and in healthy controls ( n =45) using ELISA and electrochemiluminescence assays. We also investigated other proteins known to interact with CD44, such as osteopontin and the matrix metalloproteinases MMP1, MMP3 and MMP9. Results The suicide attempters had higher CSF levels of HA ( p =.003) and MMP9 ( p =.004). The CSF levels of HA correlated with BBB-permeability (rho=0.410, p |
| doi_str_mv | 10.1016/j.jad.2015.12.069 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_swepu</sourceid><recordid>TN_cdi_swepub_primary_oai_swepub_ki_se_507832</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><els_id>S016503271531168X</els_id><sourcerecordid>1762964748</sourcerecordid><originalsourceid>FETCH-LOGICAL-c553t-63923eeff4cf4ce250b30370d5a1b3b4c1e3696f79d66987cf10d93ed7d38e863</originalsourceid><addsrcrecordid>eNp9kstu1DAUhiMEokPhAdigLNnM4EtsJ0JCqqblIo3EgoLYWb6cdDz1TIKdtJod78AL8Gw8CSfM0AUSlWLFib7_c6LzF8VzShaUUPlqs9gYv2CEigVlCyKbB8WMCsXnTFD1sJghI-aEM3VSPMl5QwgiijwuTphUjWRczIqfl2sol-dVVcZwZXa-XO9NHFO3C640Lvgy5BIi3JgBcL8rB8QdJLCpy33YmVi2cUSsa8s8BgxAaYYBtv0AKZeTEAUm586FP4rbMKzR4xKYjI82dp3_9f2HTQbl1qQUIJU9pC0YG2IY9k-LR62JGZ4d76fF57cXl8v389XHdx-WZ6u5E4IPc8kbxgHatnJ4ARPEcsIV8cJQy23lKHDZyFY1XsqmVq6lxDccvPK8hlry02J-8OZb6Eer-xS2Ju11Z4I-vrrGHWhBVM0Z8qv_8nHscVlcU0BJ4WyrvG5bRXUlqlrXrjGa29ZWtWds-tL7jj8PX850l650DKOmTEhZI__ywPep-zZCHvQ2ZAcxmh10Y9ZUSdbISlUTSg-ow5nlBO2dnBI99UhvNPZITz1CvcaSYObFUT_aLfi7xN_iIPD6AADO5AaHprMLsHPgQwI3aN-Fe_Vv_km7GLByJl7DHvKmGxNWC_9CZwzoT1ORpx5TwSmV9Vf-G49E8d4</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1762964748</pqid></control><display><type>article</type><title>The CD44 ligand hyaluronic acid is elevated in the cerebrospinal fluid of suicide attempters and is associated with increased blood–brain barrier permeability</title><source>MEDLINE</source><source>Elsevier ScienceDirect Journals</source><creator>Ventorp, F ; Barzilay, R ; Erhardt, S ; Samuelsson, M ; Träskman-Bendz, L ; Janelidze, S ; Weizman, A ; Offen, D ; Brundin, L</creator><creatorcontrib>Ventorp, F ; Barzilay, R ; Erhardt, S ; Samuelsson, M ; Träskman-Bendz, L ; Janelidze, S ; Weizman, A ; Offen, D ; Brundin, L</creatorcontrib><description>Abstract Background The glycosaminoglycan hyaluronic acid (HA) is an important component of the extracellular matrix (ECM) in the brain. CD44 is a cell adhesion molecule that binds to HA in the ECM and is present on astrocytes, microglia and certain neurons. Cell adhesion molecules have been reported to be involved in anxiety and mood disorders. CD44 levels are decreased in the cerebrospinal fluid (CSF) of depressed individuals, and the CD44 gene has been identified in brain GWAS studies as a possible risk gene for suicidal behavior. Method We measured the CSF levels of HA and the soluble CD44 (sCD44) in suicide attempters ( n =94) and in healthy controls ( n =45) using ELISA and electrochemiluminescence assays. We also investigated other proteins known to interact with CD44, such as osteopontin and the matrix metalloproteinases MMP1, MMP3 and MMP9. Results The suicide attempters had higher CSF levels of HA ( p =.003) and MMP9 ( p =.004). The CSF levels of HA correlated with BBB-permeability (rho=0.410, p <.001) and MMP9 correlated with sCD44 levels (rho=0.260, p =.005). Limitations Other relevant biological contributors to suicidal behavior is not addressed in parallel to the specific role of CD44-HA signaling. The gender distribution of the patients from whom CSF was analyzed was uneven. Conclusions Increased BBB-permeability and HA levels might be a results of increased neuroinflammation and can play a role in the pathobiology of suicidal behavior. The CD44 signaling pathway might be considered a novel target for intervention in mood disorders.</description><identifier>ISSN: 0165-0327</identifier><identifier>ISSN: 1573-2517</identifier><identifier>EISSN: 1573-2517</identifier><identifier>DOI: 10.1016/j.jad.2015.12.069</identifier><identifier>PMID: 26796235</identifier><language>eng</language><publisher>Netherlands: Elsevier B.V</publisher><subject>Adult ; Blood-Brain Barrier - metabolism ; Case-Control Studies ; CD44 ; Clinical Medicine ; CSF ; Female ; Humans ; Hyaluronan Receptors - cerebrospinal fluid ; Hyaluronan Receptors - metabolism ; Hyaluronic acid ; Hyaluronic Acid - cerebrospinal fluid ; Hyaluronic Acid - metabolism ; Inflammation ; Klinisk medicin ; Male ; Matrix Metalloproteinase 1 - cerebrospinal fluid ; Matrix Metalloproteinase 3 - cerebrospinal fluid ; Matrix Metalloproteinase 9 - cerebrospinal fluid ; Medical and Health Sciences ; Medicin och hälsovetenskap ; MMP9 ; Osteopontin - cerebrospinal fluid ; Permeability ; Psychiatry ; Psykiatri ; Suicide ; Suicide, Attempted</subject><ispartof>Journal of affective disorders, 2016-03, Vol.193, p.349-354</ispartof><rights>Elsevier B.V.</rights><rights>2016 Elsevier B.V.</rights><rights>Copyright © 2016 Elsevier B.V. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c553t-63923eeff4cf4ce250b30370d5a1b3b4c1e3696f79d66987cf10d93ed7d38e863</citedby><cites>FETCH-LOGICAL-c553t-63923eeff4cf4ce250b30370d5a1b3b4c1e3696f79d66987cf10d93ed7d38e863</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S016503271531168X$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>230,314,776,780,881,3537,27901,27902,65306</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/26796235$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttps://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-125668$$DView record from Swedish Publication Index$$Hfree_for_read</backlink><backlink>$$Uhttps://lup.lub.lu.se/record/8576654$$DView record from Swedish Publication Index$$Hfree_for_read</backlink><backlink>$$Uhttp://kipublications.ki.se/Default.aspx?queryparsed=id:132905279$$DView record from Swedish Publication Index$$Hfree_for_read</backlink></links><search><creatorcontrib>Ventorp, F</creatorcontrib><creatorcontrib>Barzilay, R</creatorcontrib><creatorcontrib>Erhardt, S</creatorcontrib><creatorcontrib>Samuelsson, M</creatorcontrib><creatorcontrib>Träskman-Bendz, L</creatorcontrib><creatorcontrib>Janelidze, S</creatorcontrib><creatorcontrib>Weizman, A</creatorcontrib><creatorcontrib>Offen, D</creatorcontrib><creatorcontrib>Brundin, L</creatorcontrib><title>The CD44 ligand hyaluronic acid is elevated in the cerebrospinal fluid of suicide attempters and is associated with increased blood–brain barrier permeability</title><title>Journal of affective disorders</title><addtitle>J Affect Disord</addtitle><description>Abstract Background The glycosaminoglycan hyaluronic acid (HA) is an important component of the extracellular matrix (ECM) in the brain. CD44 is a cell adhesion molecule that binds to HA in the ECM and is present on astrocytes, microglia and certain neurons. Cell adhesion molecules have been reported to be involved in anxiety and mood disorders. CD44 levels are decreased in the cerebrospinal fluid (CSF) of depressed individuals, and the CD44 gene has been identified in brain GWAS studies as a possible risk gene for suicidal behavior. Method We measured the CSF levels of HA and the soluble CD44 (sCD44) in suicide attempters ( n =94) and in healthy controls ( n =45) using ELISA and electrochemiluminescence assays. We also investigated other proteins known to interact with CD44, such as osteopontin and the matrix metalloproteinases MMP1, MMP3 and MMP9. Results The suicide attempters had higher CSF levels of HA ( p =.003) and MMP9 ( p =.004). The CSF levels of HA correlated with BBB-permeability (rho=0.410, p <.001) and MMP9 correlated with sCD44 levels (rho=0.260, p =.005). Limitations Other relevant biological contributors to suicidal behavior is not addressed in parallel to the specific role of CD44-HA signaling. The gender distribution of the patients from whom CSF was analyzed was uneven. Conclusions Increased BBB-permeability and HA levels might be a results of increased neuroinflammation and can play a role in the pathobiology of suicidal behavior. The CD44 signaling pathway might be considered a novel target for intervention in mood disorders.</description><subject>Adult</subject><subject>Blood-Brain Barrier - metabolism</subject><subject>Case-Control Studies</subject><subject>CD44</subject><subject>Clinical Medicine</subject><subject>CSF</subject><subject>Female</subject><subject>Humans</subject><subject>Hyaluronan Receptors - cerebrospinal fluid</subject><subject>Hyaluronan Receptors - metabolism</subject><subject>Hyaluronic acid</subject><subject>Hyaluronic Acid - cerebrospinal fluid</subject><subject>Hyaluronic Acid - metabolism</subject><subject>Inflammation</subject><subject>Klinisk medicin</subject><subject>Male</subject><subject>Matrix Metalloproteinase 1 - cerebrospinal fluid</subject><subject>Matrix Metalloproteinase 3 - cerebrospinal fluid</subject><subject>Matrix Metalloproteinase 9 - cerebrospinal fluid</subject><subject>Medical and Health Sciences</subject><subject>Medicin och hälsovetenskap</subject><subject>MMP9</subject><subject>Osteopontin - cerebrospinal fluid</subject><subject>Permeability</subject><subject>Psychiatry</subject><subject>Psykiatri</subject><subject>Suicide</subject><subject>Suicide, Attempted</subject><issn>0165-0327</issn><issn>1573-2517</issn><issn>1573-2517</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2016</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kstu1DAUhiMEokPhAdigLNnM4EtsJ0JCqqblIo3EgoLYWb6cdDz1TIKdtJod78AL8Gw8CSfM0AUSlWLFib7_c6LzF8VzShaUUPlqs9gYv2CEigVlCyKbB8WMCsXnTFD1sJghI-aEM3VSPMl5QwgiijwuTphUjWRczIqfl2sol-dVVcZwZXa-XO9NHFO3C640Lvgy5BIi3JgBcL8rB8QdJLCpy33YmVi2cUSsa8s8BgxAaYYBtv0AKZeTEAUm586FP4rbMKzR4xKYjI82dp3_9f2HTQbl1qQUIJU9pC0YG2IY9k-LR62JGZ4d76fF57cXl8v389XHdx-WZ6u5E4IPc8kbxgHatnJ4ARPEcsIV8cJQy23lKHDZyFY1XsqmVq6lxDccvPK8hlry02J-8OZb6Eer-xS2Ju11Z4I-vrrGHWhBVM0Z8qv_8nHscVlcU0BJ4WyrvG5bRXUlqlrXrjGa29ZWtWds-tL7jj8PX850l650DKOmTEhZI__ywPep-zZCHvQ2ZAcxmh10Y9ZUSdbISlUTSg-ow5nlBO2dnBI99UhvNPZITz1CvcaSYObFUT_aLfi7xN_iIPD6AADO5AaHprMLsHPgQwI3aN-Fe_Vv_km7GLByJl7DHvKmGxNWC_9CZwzoT1ORpx5TwSmV9Vf-G49E8d4</recordid><startdate>20160315</startdate><enddate>20160315</enddate><creator>Ventorp, F</creator><creator>Barzilay, R</creator><creator>Erhardt, S</creator><creator>Samuelsson, M</creator><creator>Träskman-Bendz, L</creator><creator>Janelidze, S</creator><creator>Weizman, A</creator><creator>Offen, D</creator><creator>Brundin, L</creator><general>Elsevier B.V</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>ADTPV</scope><scope>AOWAS</scope><scope>DG8</scope><scope>D95</scope></search><sort><creationdate>20160315</creationdate><title>The CD44 ligand hyaluronic acid is elevated in the cerebrospinal fluid of suicide attempters and is associated with increased blood–brain barrier permeability</title><author>Ventorp, F ; Barzilay, R ; Erhardt, S ; Samuelsson, M ; Träskman-Bendz, L ; Janelidze, S ; Weizman, A ; Offen, D ; Brundin, L</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c553t-63923eeff4cf4ce250b30370d5a1b3b4c1e3696f79d66987cf10d93ed7d38e863</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2016</creationdate><topic>Adult</topic><topic>Blood-Brain Barrier - metabolism</topic><topic>Case-Control Studies</topic><topic>CD44</topic><topic>Clinical Medicine</topic><topic>CSF</topic><topic>Female</topic><topic>Humans</topic><topic>Hyaluronan Receptors - cerebrospinal fluid</topic><topic>Hyaluronan Receptors - metabolism</topic><topic>Hyaluronic acid</topic><topic>Hyaluronic Acid - cerebrospinal fluid</topic><topic>Hyaluronic Acid - metabolism</topic><topic>Inflammation</topic><topic>Klinisk medicin</topic><topic>Male</topic><topic>Matrix Metalloproteinase 1 - cerebrospinal fluid</topic><topic>Matrix Metalloproteinase 3 - cerebrospinal fluid</topic><topic>Matrix Metalloproteinase 9 - cerebrospinal fluid</topic><topic>Medical and Health Sciences</topic><topic>Medicin och hälsovetenskap</topic><topic>MMP9</topic><topic>Osteopontin - cerebrospinal fluid</topic><topic>Permeability</topic><topic>Psychiatry</topic><topic>Psykiatri</topic><topic>Suicide</topic><topic>Suicide, Attempted</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Ventorp, F</creatorcontrib><creatorcontrib>Barzilay, R</creatorcontrib><creatorcontrib>Erhardt, S</creatorcontrib><creatorcontrib>Samuelsson, M</creatorcontrib><creatorcontrib>Träskman-Bendz, L</creatorcontrib><creatorcontrib>Janelidze, S</creatorcontrib><creatorcontrib>Weizman, A</creatorcontrib><creatorcontrib>Offen, D</creatorcontrib><creatorcontrib>Brundin, L</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>SwePub</collection><collection>SwePub Articles</collection><collection>SWEPUB Linköpings universitet</collection><collection>SWEPUB Lunds universitet</collection><jtitle>Journal of affective disorders</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Ventorp, F</au><au>Barzilay, R</au><au>Erhardt, S</au><au>Samuelsson, M</au><au>Träskman-Bendz, L</au><au>Janelidze, S</au><au>Weizman, A</au><au>Offen, D</au><au>Brundin, L</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The CD44 ligand hyaluronic acid is elevated in the cerebrospinal fluid of suicide attempters and is associated with increased blood–brain barrier permeability</atitle><jtitle>Journal of affective disorders</jtitle><addtitle>J Affect Disord</addtitle><date>2016-03-15</date><risdate>2016</risdate><volume>193</volume><spage>349</spage><epage>354</epage><pages>349-354</pages><issn>0165-0327</issn><issn>1573-2517</issn><eissn>1573-2517</eissn><abstract>Abstract Background The glycosaminoglycan hyaluronic acid (HA) is an important component of the extracellular matrix (ECM) in the brain. CD44 is a cell adhesion molecule that binds to HA in the ECM and is present on astrocytes, microglia and certain neurons. Cell adhesion molecules have been reported to be involved in anxiety and mood disorders. CD44 levels are decreased in the cerebrospinal fluid (CSF) of depressed individuals, and the CD44 gene has been identified in brain GWAS studies as a possible risk gene for suicidal behavior. Method We measured the CSF levels of HA and the soluble CD44 (sCD44) in suicide attempters ( n =94) and in healthy controls ( n =45) using ELISA and electrochemiluminescence assays. We also investigated other proteins known to interact with CD44, such as osteopontin and the matrix metalloproteinases MMP1, MMP3 and MMP9. Results The suicide attempters had higher CSF levels of HA ( p =.003) and MMP9 ( p =.004). The CSF levels of HA correlated with BBB-permeability (rho=0.410, p <.001) and MMP9 correlated with sCD44 levels (rho=0.260, p =.005). Limitations Other relevant biological contributors to suicidal behavior is not addressed in parallel to the specific role of CD44-HA signaling. The gender distribution of the patients from whom CSF was analyzed was uneven. Conclusions Increased BBB-permeability and HA levels might be a results of increased neuroinflammation and can play a role in the pathobiology of suicidal behavior. The CD44 signaling pathway might be considered a novel target for intervention in mood disorders.</abstract><cop>Netherlands</cop><pub>Elsevier B.V</pub><pmid>26796235</pmid><doi>10.1016/j.jad.2015.12.069</doi><tpages>6</tpages></addata></record> |
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| ispartof | Journal of affective disorders, 2016-03, Vol.193, p.349-354 |
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| source | MEDLINE; Elsevier ScienceDirect Journals |
| subjects | Adult Blood-Brain Barrier - metabolism Case-Control Studies CD44 Clinical Medicine CSF Female Humans Hyaluronan Receptors - cerebrospinal fluid Hyaluronan Receptors - metabolism Hyaluronic acid Hyaluronic Acid - cerebrospinal fluid Hyaluronic Acid - metabolism Inflammation Klinisk medicin Male Matrix Metalloproteinase 1 - cerebrospinal fluid Matrix Metalloproteinase 3 - cerebrospinal fluid Matrix Metalloproteinase 9 - cerebrospinal fluid Medical and Health Sciences Medicin och hälsovetenskap MMP9 Osteopontin - cerebrospinal fluid Permeability Psychiatry Psykiatri Suicide Suicide, Attempted |
| title | The CD44 ligand hyaluronic acid is elevated in the cerebrospinal fluid of suicide attempters and is associated with increased blood–brain barrier permeability |
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