Spatial visualization of comprehensive brain neurotransmitter systems and neuroactive substances by selective in situ chemical derivatization mass spectrometry imaging
Molecule-specific techniques such as MALDI and desorption electrospray ionization mass spectrometry imaging enable direct and simultaneous mapping of biomolecules in tissue sections in a single experiment. However, neurotransmitter imaging in the complex environment of biological samples remains cha...
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| Veröffentlicht in: | Nature protocols 2021-07, Vol.16 (7), p.3298-3321 |
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| creator | Shariatgorji, Reza Nilsson, Anna Fridjonsdottir, Elva Strittmatter, Nicole Dannhorn, Andreas Svenningsson, Per Goodwin, Richard J. A. Odell, Luke R. Andrén, Per E. |
| description | Molecule-specific techniques such as MALDI and desorption electrospray ionization mass spectrometry imaging enable direct and simultaneous mapping of biomolecules in tissue sections in a single experiment. However, neurotransmitter imaging in the complex environment of biological samples remains challenging. Our covalent charge-tagging approach using on-tissue chemical derivatization of primary and secondary amines and phenolic hydroxyls enables comprehensive mapping of neurotransmitter networks. Here, we present robust and easy-to-use chemical derivatization protocols that facilitate quantitative and simultaneous molecular imaging of complete neurotransmitter systems and drugs in diverse biological tissue sections with high lateral resolution. This is currently not possible with any other imaging technique. The protocol, using fluoromethylpyridinium and pyrylium reagents, describes all steps from tissue preparation (~1 h), chemical derivatization (1–2 h), data collection (timing depends on the number of samples and lateral resolution) and data analysis and interpretation. The specificity of the chemical reaction can also help users identify unknown chemical identities. Our protocol can reveal the cellular locations in which signaling molecules act and thus shed light on the complex responses that occur after the administration of drugs or during the course of a disease.
This protocol describes strategies for in situ chemical derivatization and simultaneous quantitative imaging of multiple neurotransmitters and their precursors and metabolites in brain tissue sections using MALDI and desorption electrospray ionization mass spectrometry imaging. |
| doi_str_mv | 10.1038/s41596-021-00538-w |
| format | Article |
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This protocol describes strategies for in situ chemical derivatization and simultaneous quantitative imaging of multiple neurotransmitters and their precursors and metabolites in brain tissue sections using MALDI and desorption electrospray ionization mass spectrometry imaging.</description><identifier>ISSN: 1754-2189</identifier><identifier>ISSN: 1750-2799</identifier><identifier>EISSN: 1750-2799</identifier><identifier>DOI: 10.1038/s41596-021-00538-w</identifier><identifier>PMID: 34075230</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>631/154/436 ; 631/1647/245/2160 ; 631/378/1689/364 ; 631/378/340 ; Amines ; Analytical Chemistry ; Animals ; Biological properties ; Biological samples ; Biological Techniques ; Biomedical and Life Sciences ; Biomolecules ; Brain ; Brain - diagnostic imaging ; Brain - metabolism ; Chemical reactions ; Computational Biology/Bioinformatics ; Data analysis ; Data collection ; Desorption ; Drugs ; Electrospraying ; Imaging techniques ; Ionization ; Ions ; Life Sciences ; Limit of Detection ; Male ; Mapping ; Marking and tracking techniques ; Mass spectrometry ; Mass spectroscopy ; Medical imaging ; Medicin och hälsovetenskap ; Metabolites ; Methods ; Microarrays ; Neuroimaging ; Neurological research ; Neurotransmitter Agents - metabolism ; Neurotransmitters ; Optical Imaging ; Organic Chemistry ; Phenolic compounds ; Phenols ; Protocol ; Rats ; Rats, Sprague-Dawley ; Reagents ; Reference Standards ; Scientific imaging ; Spectrometry, Mass, Electrospray Ionization - methods ; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization ; Spectroscopy ; Tissues</subject><ispartof>Nature protocols, 2021-07, Vol.16 (7), p.3298-3321</ispartof><rights>The Author(s), under exclusive licence to Springer Nature Limited 2021</rights><rights>COPYRIGHT 2021 Nature Publishing Group</rights><rights>The Author(s), under exclusive licence to Springer Nature Limited 2021.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c637t-d55b3b4c5bd842dc4ad06db2009e9c3d4ef3ce716509398a3567d90e975057043</citedby><cites>FETCH-LOGICAL-c637t-d55b3b4c5bd842dc4ad06db2009e9c3d4ef3ce716509398a3567d90e975057043</cites><orcidid>0000-0001-9484-0921 ; 0000-0002-4062-7743 ; 0000-0001-5699-8488 ; 0000-0002-1087-4057 ; 0000-0003-1277-9608</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,780,784,885,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/34075230$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttps://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-454111$$DView record from Swedish Publication Index$$Hfree_for_read</backlink><backlink>$$Uhttp://kipublications.ki.se/Default.aspx?queryparsed=id:146756537$$DView record from Swedish Publication Index$$Hfree_for_read</backlink></links><search><creatorcontrib>Shariatgorji, Reza</creatorcontrib><creatorcontrib>Nilsson, Anna</creatorcontrib><creatorcontrib>Fridjonsdottir, Elva</creatorcontrib><creatorcontrib>Strittmatter, Nicole</creatorcontrib><creatorcontrib>Dannhorn, Andreas</creatorcontrib><creatorcontrib>Svenningsson, Per</creatorcontrib><creatorcontrib>Goodwin, Richard J. A.</creatorcontrib><creatorcontrib>Odell, Luke R.</creatorcontrib><creatorcontrib>Andrén, Per E.</creatorcontrib><title>Spatial visualization of comprehensive brain neurotransmitter systems and neuroactive substances by selective in situ chemical derivatization mass spectrometry imaging</title><title>Nature protocols</title><addtitle>Nat Protoc</addtitle><addtitle>Nat Protoc</addtitle><description>Molecule-specific techniques such as MALDI and desorption electrospray ionization mass spectrometry imaging enable direct and simultaneous mapping of biomolecules in tissue sections in a single experiment. However, neurotransmitter imaging in the complex environment of biological samples remains challenging. Our covalent charge-tagging approach using on-tissue chemical derivatization of primary and secondary amines and phenolic hydroxyls enables comprehensive mapping of neurotransmitter networks. Here, we present robust and easy-to-use chemical derivatization protocols that facilitate quantitative and simultaneous molecular imaging of complete neurotransmitter systems and drugs in diverse biological tissue sections with high lateral resolution. This is currently not possible with any other imaging technique. The protocol, using fluoromethylpyridinium and pyrylium reagents, describes all steps from tissue preparation (~1 h), chemical derivatization (1–2 h), data collection (timing depends on the number of samples and lateral resolution) and data analysis and interpretation. The specificity of the chemical reaction can also help users identify unknown chemical identities. Our protocol can reveal the cellular locations in which signaling molecules act and thus shed light on the complex responses that occur after the administration of drugs or during the course of a disease.
This protocol describes strategies for in situ chemical derivatization and simultaneous quantitative imaging of multiple neurotransmitters and their precursors and metabolites in brain tissue sections using MALDI and desorption electrospray ionization mass spectrometry imaging.</description><subject>631/154/436</subject><subject>631/1647/245/2160</subject><subject>631/378/1689/364</subject><subject>631/378/340</subject><subject>Amines</subject><subject>Analytical Chemistry</subject><subject>Animals</subject><subject>Biological properties</subject><subject>Biological samples</subject><subject>Biological Techniques</subject><subject>Biomedical and Life Sciences</subject><subject>Biomolecules</subject><subject>Brain</subject><subject>Brain - diagnostic imaging</subject><subject>Brain - metabolism</subject><subject>Chemical reactions</subject><subject>Computational Biology/Bioinformatics</subject><subject>Data analysis</subject><subject>Data collection</subject><subject>Desorption</subject><subject>Drugs</subject><subject>Electrospraying</subject><subject>Imaging techniques</subject><subject>Ionization</subject><subject>Ions</subject><subject>Life Sciences</subject><subject>Limit of Detection</subject><subject>Male</subject><subject>Mapping</subject><subject>Marking and tracking techniques</subject><subject>Mass spectrometry</subject><subject>Mass spectroscopy</subject><subject>Medical imaging</subject><subject>Medicin och hälsovetenskap</subject><subject>Metabolites</subject><subject>Methods</subject><subject>Microarrays</subject><subject>Neuroimaging</subject><subject>Neurological research</subject><subject>Neurotransmitter Agents - metabolism</subject><subject>Neurotransmitters</subject><subject>Optical Imaging</subject><subject>Organic Chemistry</subject><subject>Phenolic compounds</subject><subject>Phenols</subject><subject>Protocol</subject><subject>Rats</subject><subject>Rats, Sprague-Dawley</subject><subject>Reagents</subject><subject>Reference Standards</subject><subject>Scientific imaging</subject><subject>Spectrometry, Mass, Electrospray Ionization - methods</subject><subject>Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization</subject><subject>Spectroscopy</subject><subject>Tissues</subject><issn>1754-2189</issn><issn>1750-2799</issn><issn>1750-2799</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</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>eNp9k89u1DAQxiMEoqXwAhxQJC4gSLFjO06Oq-VfpQokWuBoOc7s1iVxth6ny_JCvCZOs221iKIc7Ix_30w8ky9JnlJySAkr3yCnoioyktOMEMHKbH0v2adSkCyXVXX_as-znJbVXvII8ZwQLlkhHyZ7jBMpckb2k98nKx2sbtNLi4Nu7a_41ru0X6Sm71YezsChvYS09tq61MHg--C1w86GAD7FDQboMNWumQ61CSOOQ41BOwOY1psUoYUpHnOgDUNqzqCzJpZtwNvLWHNbt9OIKa4i7fsOgt-kttNL65aPkwcL3SI82a4Hydf3707nH7Pjzx-O5rPjzBRMhqwRomY1N6JuSp43huuGFE2dE1JBZVjDYcEMSFoIUrGq1EwUsqkIVLFrQhLODpJsyotrWA21Wvn4AX6jem3VNvQj7kDxggpRRr66k1_5vrkVXQspL6QoBJNR-_pO7Vv7baZ6v1TDoLjglNKIv5jwmPdiAAyqs2igbbWDfkCVC1ZwmY-_wkHy_C_0vB-8i42LFK-4LPOc31JL3YKybjGO1oxJ1awoZCk5oeMND_9BxacZR9g7WNgY3xG83BFEJsDPsNQDojo6-bLLvrqbnZ1-n3_apfOJNr5H9LC4aRklarSEmiyhoiXUlSXUOoqebXsx1B00N5JrD0SAbccQj9wS_G2z_pP2D0afGsY</recordid><startdate>20210701</startdate><enddate>20210701</enddate><creator>Shariatgorji, Reza</creator><creator>Nilsson, Anna</creator><creator>Fridjonsdottir, Elva</creator><creator>Strittmatter, Nicole</creator><creator>Dannhorn, Andreas</creator><creator>Svenningsson, Per</creator><creator>Goodwin, Richard J. 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A.</au><au>Odell, Luke R.</au><au>Andrén, Per E.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Spatial visualization of comprehensive brain neurotransmitter systems and neuroactive substances by selective in situ chemical derivatization mass spectrometry imaging</atitle><jtitle>Nature protocols</jtitle><stitle>Nat Protoc</stitle><addtitle>Nat Protoc</addtitle><date>2021-07-01</date><risdate>2021</risdate><volume>16</volume><issue>7</issue><spage>3298</spage><epage>3321</epage><pages>3298-3321</pages><issn>1754-2189</issn><issn>1750-2799</issn><eissn>1750-2799</eissn><abstract>Molecule-specific techniques such as MALDI and desorption electrospray ionization mass spectrometry imaging enable direct and simultaneous mapping of biomolecules in tissue sections in a single experiment. However, neurotransmitter imaging in the complex environment of biological samples remains challenging. Our covalent charge-tagging approach using on-tissue chemical derivatization of primary and secondary amines and phenolic hydroxyls enables comprehensive mapping of neurotransmitter networks. Here, we present robust and easy-to-use chemical derivatization protocols that facilitate quantitative and simultaneous molecular imaging of complete neurotransmitter systems and drugs in diverse biological tissue sections with high lateral resolution. This is currently not possible with any other imaging technique. The protocol, using fluoromethylpyridinium and pyrylium reagents, describes all steps from tissue preparation (~1 h), chemical derivatization (1–2 h), data collection (timing depends on the number of samples and lateral resolution) and data analysis and interpretation. The specificity of the chemical reaction can also help users identify unknown chemical identities. Our protocol can reveal the cellular locations in which signaling molecules act and thus shed light on the complex responses that occur after the administration of drugs or during the course of a disease.
This protocol describes strategies for in situ chemical derivatization and simultaneous quantitative imaging of multiple neurotransmitters and their precursors and metabolites in brain tissue sections using MALDI and desorption electrospray ionization mass spectrometry imaging.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>34075230</pmid><doi>10.1038/s41596-021-00538-w</doi><tpages>24</tpages><orcidid>https://orcid.org/0000-0001-9484-0921</orcidid><orcidid>https://orcid.org/0000-0002-4062-7743</orcidid><orcidid>https://orcid.org/0000-0001-5699-8488</orcidid><orcidid>https://orcid.org/0000-0002-1087-4057</orcidid><orcidid>https://orcid.org/0000-0003-1277-9608</orcidid></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1754-2189 |
| ispartof | Nature protocols, 2021-07, Vol.16 (7), p.3298-3321 |
| issn | 1754-2189 1750-2799 1750-2799 |
| language | eng |
| recordid | cdi_swepub_primary_oai_swepub_ki_se_461558 |
| source | MEDLINE; Nature; Alma/SFX Local Collection |
| subjects | 631/154/436 631/1647/245/2160 631/378/1689/364 631/378/340 Amines Analytical Chemistry Animals Biological properties Biological samples Biological Techniques Biomedical and Life Sciences Biomolecules Brain Brain - diagnostic imaging Brain - metabolism Chemical reactions Computational Biology/Bioinformatics Data analysis Data collection Desorption Drugs Electrospraying Imaging techniques Ionization Ions Life Sciences Limit of Detection Male Mapping Marking and tracking techniques Mass spectrometry Mass spectroscopy Medical imaging Medicin och hälsovetenskap Metabolites Methods Microarrays Neuroimaging Neurological research Neurotransmitter Agents - metabolism Neurotransmitters Optical Imaging Organic Chemistry Phenolic compounds Phenols Protocol Rats Rats, Sprague-Dawley Reagents Reference Standards Scientific imaging Spectrometry, Mass, Electrospray Ionization - methods Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization Spectroscopy Tissues |
| title | Spatial visualization of comprehensive brain neurotransmitter systems and neuroactive substances by selective in situ chemical derivatization mass spectrometry imaging |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-20T13%3A01%3A58IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_swepu&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Spatial%20visualization%20of%20comprehensive%20brain%20neurotransmitter%20systems%20and%20neuroactive%20substances%20by%20selective%20in%20situ%20chemical%20derivatization%20mass%20spectrometry%20imaging&rft.jtitle=Nature%20protocols&rft.au=Shariatgorji,%20Reza&rft.date=2021-07-01&rft.volume=16&rft.issue=7&rft.spage=3298&rft.epage=3321&rft.pages=3298-3321&rft.issn=1754-2189&rft.eissn=1750-2799&rft_id=info:doi/10.1038/s41596-021-00538-w&rft_dat=%3Cgale_swepu%3EA667874018%3C/gale_swepu%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2549478224&rft_id=info:pmid/34075230&rft_galeid=A667874018&rfr_iscdi=true |