Interrogating the Metabolomic Profile of Amyotrophic Lateral Sclerosis in the Post-Mortem Human Brain by Infrared Matrix-Assisted Laser Desorption Electrospray Ionization (IR-MALDESI) Mass Spectrometry Imaging (MSI)
Amyotrophic lateral sclerosis (ALS) is an idiopathic, fatal neurodegenerative disease characterized by progressive loss of motor function with an average survival time of 2–5 years after diagnosis. Due to the lack of signature biomarkers and heterogenous disease phenotypes, a definitive diagnosis of...
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| Format: | Article |
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MDPI AG
2022-11-01
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| Series: | Metabolites |
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| Online Access: | https://www.mdpi.com/2218-1989/12/11/1096 |
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| author | Alexandria L. Sohn Lingyan Ping Jonathan D. Glass Nicholas T. Seyfried Emily C. Hector David C. Muddiman |
| author_facet | Alexandria L. Sohn Lingyan Ping Jonathan D. Glass Nicholas T. Seyfried Emily C. Hector David C. Muddiman |
| author_sort | Alexandria L. Sohn |
| collection | DOAJ |
| description | Amyotrophic lateral sclerosis (ALS) is an idiopathic, fatal neurodegenerative disease characterized by progressive loss of motor function with an average survival time of 2–5 years after diagnosis. Due to the lack of signature biomarkers and heterogenous disease phenotypes, a definitive diagnosis of ALS can be challenging. Comprehensive investigation of this disease is imperative to discovering unique features to expedite the diagnostic process and improve diagnostic accuracy. Here, we present untargeted metabolomics by mass spectrometry imaging (MSI) for comparing sporadic ALS (sALS) and <i>C9orf72</i> positive (C9Pos) post-mortem frontal cortex human brain tissues against a control cohort. The spatial distribution and relative abundance of metabolites were measured by infrared matrix-assisted laser desorption electrospray ionization (IR-MALDESI) MSI for association to biological pathways. Proteomic studies on the same patients were completed via LC-MS/MS in a previous study, and results were integrated with imaging metabolomics results to enhance the breadth of molecular coverage. Utilizing METASPACE annotation platform and MSiPeakfinder, nearly 300 metabolites were identified across the sixteen samples, where 25 were identified as dysregulated between disease cohorts. The dysregulated metabolites were further examined for their relevance to alanine, aspartate, and glutamate metabolism, glutathione metabolism, and arginine and proline metabolism. The dysregulated pathways discussed are consistent with reports from other ALS studies. To our knowledge, this work is the first of its kind, reporting on the investigation of ALS post-mortem human brain tissue analyzed by multiomic MSI. |
| first_indexed | 2024-03-09T18:09:21Z |
| format | Article |
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| institution | Directory Open Access Journal |
| issn | 2218-1989 |
| language | English |
| last_indexed | 2024-03-09T18:09:21Z |
| publishDate | 2022-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Metabolites |
| spelling | doaj.art-df86a412a29d4ee49b512db906f4337b2023-11-24T09:12:56ZengMDPI AGMetabolites2218-19892022-11-011211109610.3390/metabo12111096Interrogating the Metabolomic Profile of Amyotrophic Lateral Sclerosis in the Post-Mortem Human Brain by Infrared Matrix-Assisted Laser Desorption Electrospray Ionization (IR-MALDESI) Mass Spectrometry Imaging (MSI)Alexandria L. Sohn0Lingyan Ping1Jonathan D. Glass2Nicholas T. Seyfried3Emily C. Hector4David C. Muddiman5FTMS Laboratory for Human Health Research, Department of Chemistry, North Carolina State University, Raleigh, NC 27695, USAGoizueta Alzheimer’s Disease Research Center, Emory University School of Medicine, Atlanta, GA 30322, USADepartment of Neurology, Emory University School of Medicine, Atlanta, GA 30322, USAGoizueta Alzheimer’s Disease Research Center, Emory University School of Medicine, Atlanta, GA 30322, USADepartment of Statistics, North Carolina State University, Raleigh, NC 27695, USAFTMS Laboratory for Human Health Research, Department of Chemistry, North Carolina State University, Raleigh, NC 27695, USAAmyotrophic lateral sclerosis (ALS) is an idiopathic, fatal neurodegenerative disease characterized by progressive loss of motor function with an average survival time of 2–5 years after diagnosis. Due to the lack of signature biomarkers and heterogenous disease phenotypes, a definitive diagnosis of ALS can be challenging. Comprehensive investigation of this disease is imperative to discovering unique features to expedite the diagnostic process and improve diagnostic accuracy. Here, we present untargeted metabolomics by mass spectrometry imaging (MSI) for comparing sporadic ALS (sALS) and <i>C9orf72</i> positive (C9Pos) post-mortem frontal cortex human brain tissues against a control cohort. The spatial distribution and relative abundance of metabolites were measured by infrared matrix-assisted laser desorption electrospray ionization (IR-MALDESI) MSI for association to biological pathways. Proteomic studies on the same patients were completed via LC-MS/MS in a previous study, and results were integrated with imaging metabolomics results to enhance the breadth of molecular coverage. Utilizing METASPACE annotation platform and MSiPeakfinder, nearly 300 metabolites were identified across the sixteen samples, where 25 were identified as dysregulated between disease cohorts. The dysregulated metabolites were further examined for their relevance to alanine, aspartate, and glutamate metabolism, glutathione metabolism, and arginine and proline metabolism. The dysregulated pathways discussed are consistent with reports from other ALS studies. To our knowledge, this work is the first of its kind, reporting on the investigation of ALS post-mortem human brain tissue analyzed by multiomic MSI.https://www.mdpi.com/2218-1989/12/11/1096IR-MALDESI MSImass spectrometry imagingAmyotrophic lateral sclerosis (ALS)neurodegenerative diseasemultiomic |
| spellingShingle | Alexandria L. Sohn Lingyan Ping Jonathan D. Glass Nicholas T. Seyfried Emily C. Hector David C. Muddiman Interrogating the Metabolomic Profile of Amyotrophic Lateral Sclerosis in the Post-Mortem Human Brain by Infrared Matrix-Assisted Laser Desorption Electrospray Ionization (IR-MALDESI) Mass Spectrometry Imaging (MSI) Metabolites IR-MALDESI MSI mass spectrometry imaging Amyotrophic lateral sclerosis (ALS) neurodegenerative disease multiomic |
| title | Interrogating the Metabolomic Profile of Amyotrophic Lateral Sclerosis in the Post-Mortem Human Brain by Infrared Matrix-Assisted Laser Desorption Electrospray Ionization (IR-MALDESI) Mass Spectrometry Imaging (MSI) |
| title_full | Interrogating the Metabolomic Profile of Amyotrophic Lateral Sclerosis in the Post-Mortem Human Brain by Infrared Matrix-Assisted Laser Desorption Electrospray Ionization (IR-MALDESI) Mass Spectrometry Imaging (MSI) |
| title_fullStr | Interrogating the Metabolomic Profile of Amyotrophic Lateral Sclerosis in the Post-Mortem Human Brain by Infrared Matrix-Assisted Laser Desorption Electrospray Ionization (IR-MALDESI) Mass Spectrometry Imaging (MSI) |
| title_full_unstemmed | Interrogating the Metabolomic Profile of Amyotrophic Lateral Sclerosis in the Post-Mortem Human Brain by Infrared Matrix-Assisted Laser Desorption Electrospray Ionization (IR-MALDESI) Mass Spectrometry Imaging (MSI) |
| title_short | Interrogating the Metabolomic Profile of Amyotrophic Lateral Sclerosis in the Post-Mortem Human Brain by Infrared Matrix-Assisted Laser Desorption Electrospray Ionization (IR-MALDESI) Mass Spectrometry Imaging (MSI) |
| title_sort | interrogating the metabolomic profile of amyotrophic lateral sclerosis in the post mortem human brain by infrared matrix assisted laser desorption electrospray ionization ir maldesi mass spectrometry imaging msi |
| topic | IR-MALDESI MSI mass spectrometry imaging Amyotrophic lateral sclerosis (ALS) neurodegenerative disease multiomic |
| url | https://www.mdpi.com/2218-1989/12/11/1096 |
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