A derivatization and validation strategy for determining the spatial localization of endogenous amine metabolites in tissues using MALDI imaging mass spectrometry

Manier, M. L.; Spraggins, Jeffrey M.; Reyzer, M. L.; Norris, J. L.; Caprioli, R. M.

doi:10.1002/jms.3273

Cited by 12 publications

(23 citation statements)

References 32 publications

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“…Depending on the target, small tissue biopsies and/or body fluids can be taken and analyzed for changes in the lipidome. Not only can changes in the lipidome be assessed from total lipid extracts, they can also be verified in multidimensional tissue sections by MALDI-MSbased lipid imaging, providing information about the spatial localization of the alterations [32]. Dynamic changes and alteration of fluxes through lipid metabolic pathways can be followed by simultaneous treatment with stable isotopelabeled compounds.…”

Section: Lipidomics In Preclinical and Clinical Testingmentioning

confidence: 99%

Lipidomics in drug development

Dehairs

Derua

Rueda-Rincón

et al. 2015

Drug Discovery Today: Technologies

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Numerous human pathologies, including common conditions such as obesity, diabetes, cardiovascular disease, cancer, inflammatory disease and neurodegeneration, involve changes in lipid metabolism. Likewise, a growing number of drugs are being developed that directly or indirectly affect lipid metabolic pathways. Instead of classical and cumbrous radiochemical analyses, lipid profiling by mass spectrometry (MS)-based lipidomics holds great potential as companion diagnostic in several steps along the drug development process. In this review we describe some typical lipidomics set-ups and illustrate how these technologies can be implemented in target discovery, compound screening, in vitro and in vivo preclinical testing, toxicity testing of drugs, and prediction and monitoring of response.

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Section: Lipidomics In Preclinical and Clinical Testingmentioning

confidence: 99%

Lipidomics in drug development

Dehairs

Derua

Rueda-Rincón

et al. 2015

Drug Discovery Today: Technologies

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show abstract

“…In recent studies, serotonin and tryptophan metabolism have been mapped by using LC-MS and IMS techniques. 4,57,58 Gut microbiota has the ability to promote the serotonin biosynthesis and regulate bloodbrain barrier permeability for modulating the distribution and subsequent the CNS fate of serotonin. 45 The study using microbiota deficient Germ-Free mice provided a helpful insight into the effect of gut microbiota on brain.…”

Section: Serotonin and Tryptophan Catabolitesmentioning

confidence: 99%

“…Bile acids are synthesized molecules derived from cholesterol in liver and can be profiled by using LC-MS and DESI-IMS techniques. 28 Under 98 Diaz Heijtz et al, 9 Wikoff et al, 56 Reigstad et al, 75 Manier et al, 57 59 Desbonnet et al, 53 Valladares et al, 55 Braniste et al, 52 Schwarcz et al, 54 63 Robertson et al, 66 Kishino et al, 65 Eberlin et al, 67 47 Bourassa et al, 69 De Vadder et al, 73 Frost et al, 74 Macfabe 70 78 Cortez et al, 19 Ramalho et al, 81 Castro-Caldas et al, 79 Keene et al, 21 Rath et al, 28…”

Section: Bile Acidsmentioning

confidence: 99%

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Mass spectrometry‐based metabolomics: Targeting the crosstalk between gut microbiota and brain in neurodegenerative disorders

Luan

Xian

Cai

2017

Mass Spectrometry Reviews

145

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Metabolomics seeks to take a "snapshot" in a time of the levels, activities, regulation and interactions of all small molecule metabolites in response to a biological system with genetic or environmental changes. The emerging development in mass spectrometry technologies has shown promise in the discovery and quantitation of neuroactive small molecule metabolites associated with gut microbiota and brain. Significant progress has been made recently in the characterization of intermediate role of small molecule metabolites linked to neural development and neurodegenerative disorder, showing its potential in understanding the crosstalk between gut microbiota and the host brain. More evidence reveals that small molecule metabolites may play a critical role in mediating microbial effects on neurotransmission and disease development. Mass spectrometry-based metabolomics is uniquely suitable for obtaining the metabolic signals in bidirectional communication between gut microbiota and brain. In this review, we summarized major mass spectrometry technologies including liquid chromatography-mass spectrometry, gas chromatography-mass spectrometry, and imaging mass spectrometry for metabolomics studies of neurodegenerative disorders. We also reviewed the recent advances in the identification of new metabolites by mass spectrometry and metabolic pathways involved in the connection of intestinal microbiota and brain. These metabolic pathways allowed the microbiota to impact the regular function of the brain, which can in turn affect the composition of microbiota via the neurotransmitter substances. The dysfunctional interaction of this crosstalk connects neurodegenerative diseases, including Parkinson's disease, Alzheimer's disease and Huntington's disease. The mass spectrometry-based metabolomics analysis provides information for targeting dysfunctional pathways of small molecule metabolites in the development of the neurodegenerative diseases, which may be valuable for the investigation of underlying mechanism of therapeutic strategies.

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“…The overall sensitivity of MALDI-MSI can be enhanced to some extent by optimizing the type of matrix used, the matrix solvent composition [20], the method of matrix application [21], and the tissue clean up protocol [22], or by chemical derivatization [23][24][25][26][27].…”

Section: Introductionmentioning

confidence: 99%

Pyrylium Salts as Reactive Matrices for MALDI-MS Imaging of Biologically Active Primary Amines

Shariatgorji

Nilsson

Källback

et al. 2015

J. Am. Soc. Mass Spectrom.

103

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Abstract. Many neuroactive substances, including endogenous biomolecules, environmental compounds, and pharmaceuticals possess primary amine functional groups. Among these are catecholamine neurotransmitters (e.g., dopamine), many substituted phenethylamines (e.g., amphetamine), as well as amino acids and neuropeptides. In most cases, mass spectrometric (ESI and MALDI) analyses of trace amounts of such compounds are challenging because of their poor ionization properties. We present a method for chemical derivatization of primary amines by reaction with pyrylium salts that facilitates their detection by MALDI-MS and enables the imaging of primary amines in brain tissue sections. A screen of pyrylium salts revealed that the 2,4-diphenyl-pyranylium ion efficiently derivatizes primary amines and can be used as a reactive MALDI-MS matrix that induces both derivatization and desorption. MALDI-MS imaging with such matrix was used to map the localization of dopamine and amphetamine in brain tissue sections and to quantitatively map the distribution of the neurotoxin β-N-methylamino-L-alanine.

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A derivatization and validation strategy for determining the spatial localization of endogenous amine metabolites in tissues using MALDI imaging mass spectrometry

Cited by 12 publications

References 32 publications

Lipidomics in drug development

Lipidomics in drug development

Mass spectrometry‐based metabolomics: Targeting the crosstalk between gut microbiota and brain in neurodegenerative disorders

Pyrylium Salts as Reactive Matrices for MALDI-MS Imaging of Biologically Active Primary Amines

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