Mass spectrometry imaging reveals ganglioside and ceramide localization patterns during cerebellar degeneration in the Npc1−/− mouse model
Mass spectrometry imaging (MSI) is a powerful tool to perform untargeted mapping of biomolecules in situ. In the current study, we performed matrix-assisted laser desorption/ionization-mass spectrometry imaging (MALDI-MSI) to evaluate lipid changes during disease progression (asymptomatic to symptom...
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| Veröffentlicht in: | Analytical and bioanalytical chemistry 2019-09, Vol.411 (22), p.5659-5668 |
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| creator | Tobias, Fernando Pathmasiri, Koralege C. Cologna, Stephanie M. |
| description | Mass spectrometry imaging (MSI) is a powerful tool to perform untargeted mapping of biomolecules in situ. In the current study, we performed matrix-assisted laser desorption/ionization-mass spectrometry imaging (MALDI-MSI) to evaluate lipid changes during disease progression (asymptomatic to symptomatic time points) in Niemann-Pick disease, type C1 (NPC1), a cerebellar neurodegenerative, lipid storage disorder. Our data show that gangliosides GM2 and GM3 are elevated in NPC1 disease and localize in the posterior lobules of the cerebellum, which is enhanced over a time-course analysis of the disease. Further analysis of sphingolipids in negative ion mode indicated reduction of sulfatides in white matter of the cerebellum and patterned distribution and co-localization of ceramide species Cer(d36:1), HexCer(d36:1), and the ganglioside GM1(d36:1) during disease progression. Finally, a putative lipid of unknown structure demonstrated similar patterning during NPC1 cerebellar degeneration. These studies provide insight into lipid markers of neurodegeneration in NPC1 and link lipid alterations to altered pathways that lead to cell death. |
| doi_str_mv | 10.1007/s00216-019-01989-7 |
| format | Article |
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In the current study, we performed matrix-assisted laser desorption/ionization-mass spectrometry imaging (MALDI-MSI) to evaluate lipid changes during disease progression (asymptomatic to symptomatic time points) in Niemann-Pick disease, type C1 (NPC1), a cerebellar neurodegenerative, lipid storage disorder. Our data show that gangliosides GM2 and GM3 are elevated in NPC1 disease and localize in the posterior lobules of the cerebellum, which is enhanced over a time-course analysis of the disease. Further analysis of sphingolipids in negative ion mode indicated reduction of sulfatides in white matter of the cerebellum and patterned distribution and co-localization of ceramide species Cer(d36:1), HexCer(d36:1), and the ganglioside GM1(d36:1) during disease progression. Finally, a putative lipid of unknown structure demonstrated similar patterning during NPC1 cerebellar degeneration. These studies provide insight into lipid markers of neurodegeneration in NPC1 and link lipid alterations to altered pathways that lead to cell death.</description><identifier>ISSN: 1618-2642</identifier><identifier>EISSN: 1618-2650</identifier><identifier>DOI: 10.1007/s00216-019-01989-7</identifier><identifier>PMID: 31254056</identifier><language>eng</language><publisher>Berlin/Heidelberg: Springer Berlin Heidelberg</publisher><subject>ABC Highlights: authored by Rising Stars and Top Experts ; Analytical Chemistry ; Animals ; Apoptosis ; Biochemistry ; Biomolecules ; Cell death ; Ceramide ; Ceramides - metabolism ; Cerebellum ; Cerebellum - pathology ; Characterization and Evaluation of Materials ; Chemistry ; Chemistry and Materials Science ; Chromatography, Liquid - methods ; Degeneration ; Food Science ; Ganglioside GM1 ; Gangliosides ; Gangliosides - metabolism ; Imaging ; Intracellular Signaling Peptides and Proteins - genetics ; Ionization ; Ions ; Laboratory Medicine ; Lipids ; Localization ; Mapping ; Mass spectrometry ; Mass spectroscopy ; Mice ; Mice, Knockout ; Monitoring/Environmental Analysis ; Negative ions ; Neurodegeneration ; Niemann-Pick disease ; Npc1 protein ; Paper in Forefront ; Pattern formation ; Scientific imaging ; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization - methods ; Spectroscopy ; Sphingolipids ; Substantia alba ; Tandem Mass Spectrometry - methods</subject><ispartof>Analytical and bioanalytical chemistry, 2019-09, Vol.411 (22), p.5659-5668</ispartof><rights>Springer-Verlag GmbH Germany, part of Springer Nature 2019</rights><rights>Analytical and Bioanalytical Chemistry is a copyright of Springer, (2019). All Rights Reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c375t-51b61e7151618fb060c4c54bc23630bc95df95f4ac3619eb5b3e23e66d31fae13</citedby><cites>FETCH-LOGICAL-c375t-51b61e7151618fb060c4c54bc23630bc95df95f4ac3619eb5b3e23e66d31fae13</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s00216-019-01989-7$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s00216-019-01989-7$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,780,784,27924,27925,41488,42557,51319</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/31254056$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Tobias, Fernando</creatorcontrib><creatorcontrib>Pathmasiri, Koralege C.</creatorcontrib><creatorcontrib>Cologna, Stephanie M.</creatorcontrib><title>Mass spectrometry imaging reveals ganglioside and ceramide localization patterns during cerebellar degeneration in the Npc1−/− mouse model</title><title>Analytical and bioanalytical chemistry</title><addtitle>Anal Bioanal Chem</addtitle><addtitle>Anal Bioanal Chem</addtitle><description>Mass spectrometry imaging (MSI) is a powerful tool to perform untargeted mapping of biomolecules in situ. In the current study, we performed matrix-assisted laser desorption/ionization-mass spectrometry imaging (MALDI-MSI) to evaluate lipid changes during disease progression (asymptomatic to symptomatic time points) in Niemann-Pick disease, type C1 (NPC1), a cerebellar neurodegenerative, lipid storage disorder. Our data show that gangliosides GM2 and GM3 are elevated in NPC1 disease and localize in the posterior lobules of the cerebellum, which is enhanced over a time-course analysis of the disease. Further analysis of sphingolipids in negative ion mode indicated reduction of sulfatides in white matter of the cerebellum and patterned distribution and co-localization of ceramide species Cer(d36:1), HexCer(d36:1), and the ganglioside GM1(d36:1) during disease progression. Finally, a putative lipid of unknown structure demonstrated similar patterning during NPC1 cerebellar degeneration. These studies provide insight into lipid markers of neurodegeneration in NPC1 and link lipid alterations to altered pathways that lead to cell death.</description><subject>ABC Highlights: authored by Rising Stars and Top Experts</subject><subject>Analytical Chemistry</subject><subject>Animals</subject><subject>Apoptosis</subject><subject>Biochemistry</subject><subject>Biomolecules</subject><subject>Cell death</subject><subject>Ceramide</subject><subject>Ceramides - metabolism</subject><subject>Cerebellum</subject><subject>Cerebellum - pathology</subject><subject>Characterization and Evaluation of Materials</subject><subject>Chemistry</subject><subject>Chemistry and Materials Science</subject><subject>Chromatography, Liquid - methods</subject><subject>Degeneration</subject><subject>Food Science</subject><subject>Ganglioside GM1</subject><subject>Gangliosides</subject><subject>Gangliosides - metabolism</subject><subject>Imaging</subject><subject>Intracellular Signaling Peptides and Proteins - genetics</subject><subject>Ionization</subject><subject>Ions</subject><subject>Laboratory Medicine</subject><subject>Lipids</subject><subject>Localization</subject><subject>Mapping</subject><subject>Mass spectrometry</subject><subject>Mass spectroscopy</subject><subject>Mice</subject><subject>Mice, Knockout</subject><subject>Monitoring/Environmental Analysis</subject><subject>Negative ions</subject><subject>Neurodegeneration</subject><subject>Niemann-Pick disease</subject><subject>Npc1 protein</subject><subject>Paper in Forefront</subject><subject>Pattern formation</subject><subject>Scientific imaging</subject><subject>Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization - methods</subject><subject>Spectroscopy</subject><subject>Sphingolipids</subject><subject>Substantia alba</subject><subject>Tandem Mass Spectrometry - methods</subject><issn>1618-2642</issn><issn>1618-2650</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><recordid>eNp9kUFO3TAQhq0KVCjtBbqoLHXDJsVjx06yRAjaShQ2sLYcZxKCEifYCdLjBKxYcMSepM57D5C6YDH2WPr-mfH8hHwF9gMYy44CYxxUwqBYIi-S7APZBwV5wpVkO695yvfIpxBuGQOZg_pI9gRwmTKp9snTHxMCDSPayQ89Tn5F2940rWuox3s0XaCNcU3XDqGtkBpXUYve9MujG6zp2gcztYOjo5km9C7QavaLOlJYYtcZTyts0EXRmmsdnW6QXowW_j4-H8Wg_TAHjGeF3WeyW8ee-GV7H5Drs9Ork1_J-eXP3yfH54kVmZwSCaUCzEAuP6xLpphNrUxLy4USrLSFrOpC1qmxQkGBpSwFcoFKVQJqgyAOyOGm7uiHuxnDpPs22GVch3EazblkCqRkeUS__4feDrN3cbpIpXmWF6IQkeIbyvohBI-1Hn1cpF9pYHpxS2_c0tEpvXZLZ1H0bVt6LnusXiUv9kRAbIAwLktF_9b7nbL_AHXOo8I</recordid><startdate>20190901</startdate><enddate>20190901</enddate><creator>Tobias, Fernando</creator><creator>Pathmasiri, Koralege C.</creator><creator>Cologna, Stephanie M.</creator><general>Springer Berlin Heidelberg</general><general>Springer Nature 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>3V.</scope><scope>7QF</scope><scope>7QO</scope><scope>7QQ</scope><scope>7SC</scope><scope>7SE</scope><scope>7SP</scope><scope>7SR</scope><scope>7TA</scope><scope>7TB</scope><scope>7U5</scope><scope>7U7</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8BQ</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>D1I</scope><scope>DWQXO</scope><scope>F28</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H8D</scope><scope>H8G</scope><scope>HCIFZ</scope><scope>JG9</scope><scope>JQ2</scope><scope>K9.</scope><scope>KB.</scope><scope>KR7</scope><scope>L7M</scope><scope>LK8</scope><scope>L~C</scope><scope>L~D</scope><scope>M0S</scope><scope>M1P</scope><scope>M7P</scope><scope>P64</scope><scope>PDBOC</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>7X8</scope></search><sort><creationdate>20190901</creationdate><title>Mass spectrometry imaging reveals ganglioside and ceramide localization patterns during cerebellar degeneration in the Npc1−/− mouse model</title><author>Tobias, Fernando ; Pathmasiri, Koralege C. ; Cologna, Stephanie M.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c375t-51b61e7151618fb060c4c54bc23630bc95df95f4ac3619eb5b3e23e66d31fae13</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><topic>ABC Highlights: authored by Rising Stars and Top Experts</topic><topic>Analytical Chemistry</topic><topic>Animals</topic><topic>Apoptosis</topic><topic>Biochemistry</topic><topic>Biomolecules</topic><topic>Cell death</topic><topic>Ceramide</topic><topic>Ceramides - 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Academic</collection><jtitle>Analytical and bioanalytical chemistry</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Tobias, Fernando</au><au>Pathmasiri, Koralege C.</au><au>Cologna, Stephanie M.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Mass spectrometry imaging reveals ganglioside and ceramide localization patterns during cerebellar degeneration in the Npc1−/− mouse model</atitle><jtitle>Analytical and bioanalytical chemistry</jtitle><stitle>Anal Bioanal Chem</stitle><addtitle>Anal Bioanal Chem</addtitle><date>2019-09-01</date><risdate>2019</risdate><volume>411</volume><issue>22</issue><spage>5659</spage><epage>5668</epage><pages>5659-5668</pages><issn>1618-2642</issn><eissn>1618-2650</eissn><abstract>Mass spectrometry imaging (MSI) is a powerful tool to perform untargeted mapping of biomolecules in situ. In the current study, we performed matrix-assisted laser desorption/ionization-mass spectrometry imaging (MALDI-MSI) to evaluate lipid changes during disease progression (asymptomatic to symptomatic time points) in Niemann-Pick disease, type C1 (NPC1), a cerebellar neurodegenerative, lipid storage disorder. Our data show that gangliosides GM2 and GM3 are elevated in NPC1 disease and localize in the posterior lobules of the cerebellum, which is enhanced over a time-course analysis of the disease. Further analysis of sphingolipids in negative ion mode indicated reduction of sulfatides in white matter of the cerebellum and patterned distribution and co-localization of ceramide species Cer(d36:1), HexCer(d36:1), and the ganglioside GM1(d36:1) during disease progression. Finally, a putative lipid of unknown structure demonstrated similar patterning during NPC1 cerebellar degeneration. These studies provide insight into lipid markers of neurodegeneration in NPC1 and link lipid alterations to altered pathways that lead to cell death.</abstract><cop>Berlin/Heidelberg</cop><pub>Springer Berlin Heidelberg</pub><pmid>31254056</pmid><doi>10.1007/s00216-019-01989-7</doi><tpages>10</tpages></addata></record> |
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| subjects | ABC Highlights: authored by Rising Stars and Top Experts Analytical Chemistry Animals Apoptosis Biochemistry Biomolecules Cell death Ceramide Ceramides - metabolism Cerebellum Cerebellum - pathology Characterization and Evaluation of Materials Chemistry Chemistry and Materials Science Chromatography, Liquid - methods Degeneration Food Science Ganglioside GM1 Gangliosides Gangliosides - metabolism Imaging Intracellular Signaling Peptides and Proteins - genetics Ionization Ions Laboratory Medicine Lipids Localization Mapping Mass spectrometry Mass spectroscopy Mice Mice, Knockout Monitoring/Environmental Analysis Negative ions Neurodegeneration Niemann-Pick disease Npc1 protein Paper in Forefront Pattern formation Scientific imaging Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization - methods Spectroscopy Sphingolipids Substantia alba Tandem Mass Spectrometry - methods |
| title | Mass spectrometry imaging reveals ganglioside and ceramide localization patterns during cerebellar degeneration in the Npc1−/− mouse model |
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