Omega-3 and -6 Fatty Acids Alter the Membrane Lipid Composition and Vesicle Size to Regulate Exocytosis and Storage of Catecholamines.

The two essential fatty acids, alpha-linolenic acid and linoleic acid, and the higher unsaturated fatty acids synthesized from them are critical for the development and maintenance of normal brain functions. Deficiencies of these fatty acids have been shown to cause damage to the neuronal development, cognition, and locomotor function. We combined electrochemistry and imaging techniques to examine the effects of the two essential fatty acids on catecholamine release dynamics and the vesicle content as well as on the cell membrane phospholipid composition to understand how they impact exocytosis and by extension neurotransmission at the single-cell level.

Distinct Cholesterol Localization in Glioblastoma Multiforme Revealed by Mass Spectrometry Imaging.

Glioblastoma multiforme (GBM) is the most common and aggressive brain tumor in adults and is highly resistant to chemo- and radiotherapies. GBM has been associated with alterations in lipid contents, but lipid metabolism reprogramming in tumor cells is not fully elucidated. One of the key hurdles is to localize the lipid species that are correlated with tumor growth and invasion.

Mapping the Chemistry of Hair Strands by Mass Spectrometry Imaging-A Review.

Hair can record chemical information reflecting our living conditions, and, therefore, strands of hair have become a potent analytical target within the biological and forensic sciences. While early efforts focused on analyzing complete hair strands in bulk, high spatial resolution mass spectrometry imaging (MSI) has recently come to the forefront of chemical hair-strand analysis. MSI techniques offer a localized analysis, requiring fewer de-contamination procedures per default and making it possible to map the distribution of analytes on and within individual hair strands.

Combined electrochemistry and mass spectrometry imaging to interrogate the mechanism of action of modafinil, a cognition-enhancing drug, at the cellular and sub-cellular level.

Modafinil is a mild psychostimulant-like drug enhancing wakefulness, improving attention and developing performance in various cognitive tasks, but its mechanism of action is not completely understood. This is the first combination of amperometry, electrochemical cytometry and mass spectrometry to interrogate the mechanism of action of a drug, here modafinil, at cellular and sub-cellular level. We employed single-cell amperometry (SCA) and intracellular vesicle impact electrochemical cytometry (IVIEC) to investigate the alterations in exocytotic release and vesicular catecholamine storage following modafinil treatment.

Mass Spectrometry Imaging Shows Modafinil, A Student Study Drug, Changes the Lipid Composition of the Fly Brain.

Modafinil, a widely used psychoactive drug, has been shown to exert a positive impact on cognition and is used to treat sleep disorders and hyperactivity. Using time-of-flight secondary ion mass spectrometric imaging, we studied the changes of brain lipids of Drosophila melanogaster induced by modafinil to gain insight into the functional mechanism of modafinil in the brain. We found that upon modafinil treatment, the abundance of phosphatidylcholine and sphingomyelin species in the central brain of Drosophila is significantly decreased, whereas the levels of phosphatidylethanolamine and phosphatidylinositol in the brains show significant enhancement compared to the control flies.

Mass Spectrometric Imaging of Plasma Membrane Lipid Alteration Correlated with Amperometrically Measured Activity-Dependent Plasticity in Exocytosis.

The mechanism of synaptic plasticity and its link to memory formation are of interest, yet relatively obscure, especially the initial chemical change in the cell membrane following transmitter release. To understand the chemical mechanism of plasticity, we studied how repetitive stimuli regulate certain membrane lipid species to enhance exocytotic release using mass spectrometric imaging. We found that increasing high-curvature lipid species and decreasing low-curvature lipids in the cell membrane favor the formation of a longer-lasting exocytotic fusion pore, resulting in higher release fraction for individual exocytotic events.

Zinc Deficiency Leads to Lipid Changes in Drosophila Brain Similar to Cognitive-Impairing Drugs: An Imaging Mass Spectrometry Study.

Several diseases and disorders have been suggested to be associated with zinc deficiency, especially learning and memory impairment. To have better understanding about the connection between lipid changes and cognitive impairments, we investigated the effects of a zinc-chelated diet on certain brain lipids of Drosophila melanogaster by using time-of-flight secondary ion mass spectrometry (ToF-SIMS). The data revealed that there are increases in the levels of phosphatidylcholine and phosphatidylinositol in the central brains of the zinc-deficient flies compared to the control flies.

Interplay between Cocaine, Drug Removal, and Methylphenidate Reversal on Phospholipid Alterations in Brain Determined by Imaging Mass Spectrometry.

Cocaine dependence displays a broad impairment in cognitive performance including attention, learning, and memory. To obtain a better understanding of the action of cocaine in the nervous system, and the relation between phospholipids and memory, we have investigated whether phospholipids recover in the brain following cocaine removal using the fly model, . In addition, the effects of methylphenidate, a substitute medication for cocaine dependence, on fly brain lipids after cocaine abuse are also determined to see if it can rescue the lipid changes caused by cocaine.

Relative quantification of deuterated omega-3 and -6 fatty acids and their lipid turnover in PC12 cell membranes using TOF-SIMS.

Understanding FA metabolism and lipid synthesis requires a lot of information about which FAs and lipids are formed within the cells. We focused on the use of deuterated substrates of 100 μM α-linolenic acid and linoleic acid to determine the relative amounts of their converted PUFAs and specific phospholipids that are incorporated into cell plasma membranes. Time-of-flight secondary ion mass spectrometry (TOF-SIMS) was used to image and analyze lipids in model cell membranes with and without FA treatment.

Mass Spectrometry Imaging Shows Cocaine and Methylphenidate Have Opposite Effects on Major Lipids in Drosophila Brain.

Time-of-flight secondary ion mass spectrometry (ToF-SIMS) was used to study the effects of cocaine versus methylphenidate administration on both the localization and abundance of lipids in Drosophila melanogaster brain. A J105 ToF-SIMS with a 40 keV gas cluster primary ion source enabled us to probe molecular ions of biomolecules on the fly with a spatial resolution of ∼3 μm, giving us unique insights into the effect of these drugs on molecular lipids in the nervous system. Significant changes in phospholipid composition were observed in the central brain for both.