Mass spectrometry-based lipid analysis and imaging

Pathmasiri, Koralege C; Nguyen, Thu T A; Khamidova, Nigina; Cologna, Stephanie M.

doi:10.1016/bs.ctm.2021.10.005

Cited by 10 publications

(6 citation statements)

References 179 publications

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“…The MALDI matrix, a-cyano-4-hydroxycinnamic acid (CHCA), was obtained from MilliporeSigma (St. Louis, MO). The CHCA matrix is widely suitable for lipids . All solvents and other chemicals used were either reagent or high-performance liquid chromatography (HPLC) grade and purchased from Fisher Scientific (Hampton, NH), unless otherwise specified.…”

Section: Methodsmentioning

confidence: 99%

Spatial Heterogeneity of Brain Lipids in SIV-Infected Macaques Treated with Antiretroviral Therapy

White,

Gausepohl,

Wilkins

et al. 2024

J. Am. Soc. Mass Spectrom.

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Human immunodeficiency virus (HIV) infection continues to promote neurocognitive impairment, mood disorders, and brain atrophy, even in the modern era of viral suppression. Brain lipids are vulnerable to HIV-associated energetic strain and may contribute to HIV-associated neurologic dysfunction due to alterations in lipid breakdown and structural lipid composition. HIV neuropathology is region dependent, yet there has not been comprehensive characterization of the spatial heterogeneity of brain lipids during infection that possibly impacts neurologic function. To address this gap, we evaluated the spatial lipid distribution using matrix laser desorption/ionization imaging mass spectrometry (MALDI-IMS) across four brain regions (parietal cortex, midbrain, thalamus, and temporal cortex), as well as the kidney for a peripheral tissue control, in a simian immunodeficiency virus (SIV)infected rhesus macaque treated with a course of antiretroviral therapies (ARTs). We assessed lipids indicative of fat breakdown [acylcarnitines (CARs)] and critical structural lipids [phosphatidylcholines (PCs) and phosphatidylethanolamines (PEs)] across fatty acid chain lengths and degrees of unsaturation. CARs with very long-chain, polyunsaturated fatty acids (PUFAs) were more abundant across all brain regions than shorter chain, saturated, or monounsaturated species. We observed distinct brain lipid distribution patterns for the CARs and PCs. However, no clear expression patterns emerged for PEs. Surprisingly, the kidney was nearly devoid of ions corresponding to PUFAs common in brain. PEs and PCs with PUFAs had little intensity and less density than other species, and only one CAR species was observed in kidney at high intensity. Overall, our study demonstrates the stark variation in structural phospholipids and lipid-energetic intermediates present in the virally suppressed SIV-macaque brain. These findings may be useful for identifying regional vulnerabilities to damage due to brain lipid changes in people with HIV.

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Section: Methodsmentioning

confidence: 99%

Spatial Heterogeneity of Brain Lipids in SIV-Infected Macaques Treated with Antiretroviral Therapy

White,

Gausepohl,

Wilkins

et al. 2024

J. Am. Soc. Mass Spectrom.

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“…For lipid imaging on the 4800 Plus MALDI TOF/TOF Analyzer (Applied Biosystems SCIEX) and rapifleX MALDI Tissuetyper (Bruker), 1,5-diaminonaphthalene (DAN) was applied to the immobilized and dried sample via sublimation using a previously described homemade sublimation apparatus 38 , 39 . Briefly, 50 mg of DAN was dissolved in 2 mL of acetone, aspirated onto the bottom of the sublimation flask, and blow-dried using nitrogen to form a thin layer of white solid.…”

Section: Methodsmentioning

confidence: 99%

Gel-assisted mass spectrometry imaging enables sub-micrometer spatial lipidomics

Chan,

Pathmasiri,

Pierre-Jacques

et al. 2024

Nat Commun

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A technique capable of label-free detection, mass spectrometry imaging (MSI) is a powerful tool for spatial investigation of native biomolecules in intact specimens. However, MSI has often been precluded from single-cell applications due to the spatial resolution limit set forth by the physical and instrumental constraints of the method. By taking advantage of the reversible interaction between the analytes and a superabsorbent hydrogel, we have developed a sample preparation and imaging workflow named Gel-Assisted Mass Spectrometry Imaging (GAMSI) to overcome the spatial resolution limits of modern mass spectrometers. With GAMSI, we show that the spatial resolution of MALDI-MSI can be enhanced ~3-6-fold to the sub-micrometer level without changing the existing mass spectrometry hardware or analysis pipeline. This approach will vastly enhance the accessibility of MSI-based spatial analysis at the cellular scale.

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“…MALDI matrix, a-cyano-4-hydroxycinnamic acid (CHCA) was obtained from MilliporeSigma (St. Louis, MO). The CHCA matrix is widely suitable for lipids ( 49 ). All solvents and other chemicals used were either reagent or high-performance liquid chromatography (HPLC) grade and purchased from Fisher Scientific (Hampton, NH), unless otherwise specified.…”

Section: Methodsmentioning

confidence: 99%

Spatial Heterogeneity of Brain Lipids in SIV-infected Macaques Treated with Antiretroviral Therapy

White

Gausepohl

Seneviratne

et al. 2022

Preprint

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Human immunodeficiency virus infection (HIV) continues to promote neurocognitive impairment, mood disorders, and brain atrophy even in the modern era of viral suppression. Brain lipids are vulnerable to HIV-associated energetic strain and contribute to HIV-associated neurologic dysfunction due to alterations in lipid breakdown and structural lipid composition. HIV neuropathology is region dependent, yet there has not been a comprehensive spatial evaluation of brain lipids during infection that may impact neurologic function. To address this gap, we evaluated brain lipid distribution using matrix laser desorption/ionization imaging mass spectrometry (MALDI-IMS) across four brain regions (parietal cortex, midbrain, thalamus, and temporal cortex), as well as kidney for a peripheral tissue control, in a virally suppressed simian immunodeficiency virus (SIV)-infected rhesus macaque. We assessed lipids indicative of fat breakdown (acylcarnitines) and critical structural lipids (phosphatidylcholines and phosphatidylethanolamines) across fatty acid chain lengths and degrees of unsaturation. Acylcarnitines with very long-chain, polyunsaturated fatty acids were more abundant across all brain regions than shorter chain, saturated or monounsaturated species. We observed two distinct brain lipid distribution patterns for acylcarnitines and phosphatidylcholines. However, no clear expression patterns emerged for phosphatidylethanolamines. Surprisingly, acylcarnitines were largely missing in kidney, while common phosphatidylcholines and phosphatidylethanolamines were absent in kidney. Overall, our study provides substantial evidence for persistent bioenergetic changes to the brain despite viral suppression, including region-dependent mobilization of acylcarnitines for oxidation and disparities in the presence of key phospholipids necessary for maintaining proper brain structure and function. These data indicate that region-specific interventions to restore proper lipid metabolism are essential for treating HIV neurologic disease in the era of ART.

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Mass spectrometry-based lipid analysis and imaging

Cited by 10 publications

References 179 publications

Spatial Heterogeneity of Brain Lipids in SIV-Infected Macaques Treated with Antiretroviral Therapy

Spatial Heterogeneity of Brain Lipids in SIV-Infected Macaques Treated with Antiretroviral Therapy

Gel-assisted mass spectrometry imaging enables sub-micrometer spatial lipidomics

Spatial Heterogeneity of Brain Lipids in SIV-infected Macaques Treated with Antiretroviral Therapy

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