Altered ceramide acyl chain length and ceramide synthase gene expression in Parkinson's disease
ABSTRACT Genetic studies have provided increasing evidence that ceramide homeostasis plays a role in neurodegenerative diseases including Parkinson's disease (PD). It is known that the relative amounts of different ceramide molecular species, as defined by their fatty acyl chain length, regulat...
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| Veröffentlicht in: | Movement disorders 2014-04, Vol.29 (4), p.518-526 |
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| creator | Abbott, Sarah K. Li, Hongyun Muñoz, Sonia Sanz Knoch, Bianca Batterham, Marijka Murphy, Karen E. Halliday, Glenda M. Garner, Brett |
| description | ABSTRACT
Genetic studies have provided increasing evidence that ceramide homeostasis plays a role in neurodegenerative diseases including Parkinson's disease (PD). It is known that the relative amounts of different ceramide molecular species, as defined by their fatty acyl chain length, regulate ceramide function in lipid membranes and in signaling pathways. In the present study we used a comprehensive sphingolipidomic case‐control approach to determine the effects of PD on ceramide composition in postmortem brain tissue from the anterior cingulate cortex (a region with significant PD pathology) and the occipital cortex (spared in PD), also assessing mRNA expression of the major ceramide synthase genes that regulate ceramide acyl chain composition in the same tissue using quantitative PCR. In PD anterior cingulate cortex but not occipital cortex, total ceramide and sphingomyelin levels were reduced from control levels by 53% (P |
| doi_str_mv | 10.1002/mds.25729 |
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Genetic studies have provided increasing evidence that ceramide homeostasis plays a role in neurodegenerative diseases including Parkinson's disease (PD). It is known that the relative amounts of different ceramide molecular species, as defined by their fatty acyl chain length, regulate ceramide function in lipid membranes and in signaling pathways. In the present study we used a comprehensive sphingolipidomic case‐control approach to determine the effects of PD on ceramide composition in postmortem brain tissue from the anterior cingulate cortex (a region with significant PD pathology) and the occipital cortex (spared in PD), also assessing mRNA expression of the major ceramide synthase genes that regulate ceramide acyl chain composition in the same tissue using quantitative PCR. In PD anterior cingulate cortex but not occipital cortex, total ceramide and sphingomyelin levels were reduced from control levels by 53% (P < 0.001) and 42% (P < 0.001), respectively. Of the 13 ceramide and 15 sphingomyelin molecular lipid species identified and quantified, there was a significant shift in the ceramide acyl chain composition toward shorter acyl chain length in the PD anterior cingulate cortex. This PD‐associated change in ceramide acyl chain composition was accompanied by an upregulation of ceramide synthase‐1 gene expression, which we consider may represent a response to reduced ceramide levels. These data suggest a significant shift in ceramide function in lipid membranes and signaling pathways occurs in regions with PD pathology. Identifying the regulatory mechanisms precipitating this change may provide novel targets for future therapeutics. © 2013 International Parkinson and Movement Disorder Society</description><identifier>ISSN: 0885-3185</identifier><identifier>EISSN: 1531-8257</identifier><identifier>DOI: 10.1002/mds.25729</identifier><identifier>PMID: 24822250</identifier><identifier>CODEN: MOVDEA</identifier><language>eng</language><publisher>United States: Blackwell Publishing Ltd</publisher><subject>Aged ; Aged, 80 and over ; Brain - metabolism ; Brain - pathology ; ceramide ; ceramide synthase genes ; Ceramides - metabolism ; Female ; Gene Expression ; Humans ; Male ; Middle Aged ; Movement disorders ; Oxidoreductases - genetics ; Parkinson Disease - genetics ; Parkinson Disease - metabolism ; Parkinson Disease - pathology ; Parkinson's disease ; postmortem tissue analysis ; sphingolipidomics ; sphingomyelin</subject><ispartof>Movement disorders, 2014-04, Vol.29 (4), p.518-526</ispartof><rights>2013 International Parkinson and Movement Disorder Society</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4909-e6a5c3cd8c46cacc5134e8f3b1d608e2c5070264b8a69693ec7030a7192e9e573</citedby><cites>FETCH-LOGICAL-c4909-e6a5c3cd8c46cacc5134e8f3b1d608e2c5070264b8a69693ec7030a7192e9e573</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fmds.25729$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fmds.25729$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,778,782,1414,27907,27908,45557,45558</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/24822250$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Abbott, Sarah K.</creatorcontrib><creatorcontrib>Li, Hongyun</creatorcontrib><creatorcontrib>Muñoz, Sonia Sanz</creatorcontrib><creatorcontrib>Knoch, Bianca</creatorcontrib><creatorcontrib>Batterham, Marijka</creatorcontrib><creatorcontrib>Murphy, Karen E.</creatorcontrib><creatorcontrib>Halliday, Glenda M.</creatorcontrib><creatorcontrib>Garner, Brett</creatorcontrib><title>Altered ceramide acyl chain length and ceramide synthase gene expression in Parkinson's disease</title><title>Movement disorders</title><addtitle>Mov Disord</addtitle><description>ABSTRACT
Genetic studies have provided increasing evidence that ceramide homeostasis plays a role in neurodegenerative diseases including Parkinson's disease (PD). It is known that the relative amounts of different ceramide molecular species, as defined by their fatty acyl chain length, regulate ceramide function in lipid membranes and in signaling pathways. In the present study we used a comprehensive sphingolipidomic case‐control approach to determine the effects of PD on ceramide composition in postmortem brain tissue from the anterior cingulate cortex (a region with significant PD pathology) and the occipital cortex (spared in PD), also assessing mRNA expression of the major ceramide synthase genes that regulate ceramide acyl chain composition in the same tissue using quantitative PCR. In PD anterior cingulate cortex but not occipital cortex, total ceramide and sphingomyelin levels were reduced from control levels by 53% (P < 0.001) and 42% (P < 0.001), respectively. Of the 13 ceramide and 15 sphingomyelin molecular lipid species identified and quantified, there was a significant shift in the ceramide acyl chain composition toward shorter acyl chain length in the PD anterior cingulate cortex. This PD‐associated change in ceramide acyl chain composition was accompanied by an upregulation of ceramide synthase‐1 gene expression, which we consider may represent a response to reduced ceramide levels. These data suggest a significant shift in ceramide function in lipid membranes and signaling pathways occurs in regions with PD pathology. Identifying the regulatory mechanisms precipitating this change may provide novel targets for future therapeutics. © 2013 International Parkinson and Movement Disorder Society</description><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>Brain - metabolism</subject><subject>Brain - pathology</subject><subject>ceramide</subject><subject>ceramide synthase genes</subject><subject>Ceramides - metabolism</subject><subject>Female</subject><subject>Gene Expression</subject><subject>Humans</subject><subject>Male</subject><subject>Middle Aged</subject><subject>Movement disorders</subject><subject>Oxidoreductases - genetics</subject><subject>Parkinson Disease - genetics</subject><subject>Parkinson Disease - metabolism</subject><subject>Parkinson Disease - pathology</subject><subject>Parkinson's disease</subject><subject>postmortem tissue analysis</subject><subject>sphingolipidomics</subject><subject>sphingomyelin</subject><issn>0885-3185</issn><issn>1531-8257</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2014</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqF0V1LHDEUBuAgLbrVXvQPlEAvbC9G8zH5upTVasGP0q0I3oRs5qwbO5NZk1nq_vtGV6UUihAIIc954fAi9IGSPUoI2--avMeEYmYDjajgtNLl9QaNiNai4lSLLfQu51tCKBVUbqItVmvGmCAjZA_aARI02ENyXWgAO79qsZ-7EHEL8WaYYxf_-s6rOMxdBnwDETDcLxLkHPqIi__u0q8Qcx93M25ChsJ20NuZazO8f7q30eXXo5_jk-r04vjb-OC08rUhpgLphOe-0b6W3nkvKK9Bz_iUNpJoYF4QRZisp9pJIw0HrwgnTlHDwIBQfBt9XucuUn-3hDzYLmQPbesi9MtsqWTKaG6IeJ0KVvOaUaUL_fQPve2XKZZFiqKsLkfRor6slU99zglmdpFC59LKUmIfCrKlIPtYULEfnxKX0w6aF_ncSAH7a_A7tLD6f5I9O5w8R1briZAHuH-ZKF1YqbgS9ur82E5OzsbXk6tD-4P_AfdRqCc</recordid><startdate>201404</startdate><enddate>201404</enddate><creator>Abbott, Sarah K.</creator><creator>Li, Hongyun</creator><creator>Muñoz, Sonia Sanz</creator><creator>Knoch, Bianca</creator><creator>Batterham, Marijka</creator><creator>Murphy, Karen E.</creator><creator>Halliday, Glenda M.</creator><creator>Garner, Brett</creator><general>Blackwell Publishing Ltd</general><general>Wiley Subscription Services, Inc</general><scope>BSCLL</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>7TK</scope><scope>8FD</scope><scope>FR3</scope><scope>K9.</scope><scope>NAPCQ</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope></search><sort><creationdate>201404</creationdate><title>Altered ceramide acyl chain length and ceramide synthase gene expression in Parkinson's disease</title><author>Abbott, Sarah K. ; Li, Hongyun ; Muñoz, Sonia Sanz ; Knoch, Bianca ; Batterham, Marijka ; Murphy, Karen E. ; Halliday, Glenda M. ; Garner, Brett</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4909-e6a5c3cd8c46cacc5134e8f3b1d608e2c5070264b8a69693ec7030a7192e9e573</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2014</creationdate><topic>Aged</topic><topic>Aged, 80 and over</topic><topic>Brain - metabolism</topic><topic>Brain - pathology</topic><topic>ceramide</topic><topic>ceramide synthase genes</topic><topic>Ceramides - metabolism</topic><topic>Female</topic><topic>Gene Expression</topic><topic>Humans</topic><topic>Male</topic><topic>Middle Aged</topic><topic>Movement disorders</topic><topic>Oxidoreductases - genetics</topic><topic>Parkinson Disease - genetics</topic><topic>Parkinson Disease - metabolism</topic><topic>Parkinson Disease - pathology</topic><topic>Parkinson's disease</topic><topic>postmortem tissue analysis</topic><topic>sphingolipidomics</topic><topic>sphingomyelin</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Abbott, Sarah K.</creatorcontrib><creatorcontrib>Li, Hongyun</creatorcontrib><creatorcontrib>Muñoz, Sonia Sanz</creatorcontrib><creatorcontrib>Knoch, Bianca</creatorcontrib><creatorcontrib>Batterham, Marijka</creatorcontrib><creatorcontrib>Murphy, Karen E.</creatorcontrib><creatorcontrib>Halliday, Glenda M.</creatorcontrib><creatorcontrib>Garner, Brett</creatorcontrib><collection>Istex</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Neurosciences Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Premium</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Movement disorders</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Abbott, Sarah K.</au><au>Li, Hongyun</au><au>Muñoz, Sonia Sanz</au><au>Knoch, Bianca</au><au>Batterham, Marijka</au><au>Murphy, Karen E.</au><au>Halliday, Glenda M.</au><au>Garner, Brett</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Altered ceramide acyl chain length and ceramide synthase gene expression in Parkinson's disease</atitle><jtitle>Movement disorders</jtitle><addtitle>Mov Disord</addtitle><date>2014-04</date><risdate>2014</risdate><volume>29</volume><issue>4</issue><spage>518</spage><epage>526</epage><pages>518-526</pages><issn>0885-3185</issn><eissn>1531-8257</eissn><coden>MOVDEA</coden><abstract>ABSTRACT
Genetic studies have provided increasing evidence that ceramide homeostasis plays a role in neurodegenerative diseases including Parkinson's disease (PD). It is known that the relative amounts of different ceramide molecular species, as defined by their fatty acyl chain length, regulate ceramide function in lipid membranes and in signaling pathways. In the present study we used a comprehensive sphingolipidomic case‐control approach to determine the effects of PD on ceramide composition in postmortem brain tissue from the anterior cingulate cortex (a region with significant PD pathology) and the occipital cortex (spared in PD), also assessing mRNA expression of the major ceramide synthase genes that regulate ceramide acyl chain composition in the same tissue using quantitative PCR. In PD anterior cingulate cortex but not occipital cortex, total ceramide and sphingomyelin levels were reduced from control levels by 53% (P < 0.001) and 42% (P < 0.001), respectively. Of the 13 ceramide and 15 sphingomyelin molecular lipid species identified and quantified, there was a significant shift in the ceramide acyl chain composition toward shorter acyl chain length in the PD anterior cingulate cortex. This PD‐associated change in ceramide acyl chain composition was accompanied by an upregulation of ceramide synthase‐1 gene expression, which we consider may represent a response to reduced ceramide levels. These data suggest a significant shift in ceramide function in lipid membranes and signaling pathways occurs in regions with PD pathology. Identifying the regulatory mechanisms precipitating this change may provide novel targets for future therapeutics. © 2013 International Parkinson and Movement Disorder Society</abstract><cop>United States</cop><pub>Blackwell Publishing Ltd</pub><pmid>24822250</pmid><doi>10.1002/mds.25729</doi><tpages>9</tpages></addata></record> |
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| subjects | Aged Aged, 80 and over Brain - metabolism Brain - pathology ceramide ceramide synthase genes Ceramides - metabolism Female Gene Expression Humans Male Middle Aged Movement disorders Oxidoreductases - genetics Parkinson Disease - genetics Parkinson Disease - metabolism Parkinson Disease - pathology Parkinson's disease postmortem tissue analysis sphingolipidomics sphingomyelin |
| title | Altered ceramide acyl chain length and ceramide synthase gene expression in Parkinson's disease |
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