Interrogation of drug effects on the lipid composition of single cells and Drosophila brain using ToF-SIMS imaging
The papers included in this thesis describe the application of ToF-SIMS in biological samples to reveal the alterations of lipids after drug treatments. In paper I, the alterations in lipid distribution and composition induced by cocaine and methylphenidate, which cause the impairment and enhancement in cognitive performance respectively, were investigated. ToF-SIMS data were used to show that cocaine and methylphenidate have opposite effects on the relative levels of lipids in the central fly brain. To enhance our understanding about the lipid mechanisms, in paper II, I used stable deuterium-labeled omega-3 and -6 fatty acids as lipid precursors to analyze the synthesis and transportation of lipids into the plasma membrane of PC12 cells. The use of isotope-labeled fatty acids provided a tool to track the lipid turn-over as well as to measure their relative amounts. Paper III continued the work done in paper I, where experiments were performed to investigate the recovery of lipids after cocaine removal. In addition, the cognitive-enhancing drug, methylphenidate, was used to treat cocaine removal from flies to investigate the reversal of lipid changes in the brain caused by repeated-cocaine exposure. Zinc deficiency in the diet, which causes a decrease in cognitive function, was also studied in fly brain. ToF-SIMS data obtained reveal that the lipid types that change are similar to those when treated with cocaine as seen in paper IV.
ToF-SIMS opens a new approach to visualize and relatively quantify phospholipids in biological tissues and cells. In the biological model systems studied here, cognition-affecting drugs show that alterations in the distribution and composition of specific lipids is altered differently based on whether the drug enhances versus diminishes cognition. These results provide new possible targets for lipid-modifying therapies to improve the cognitive decline in drug abuse and diseases.
omega-3 and 6- fatty acids
Keywords: Mass spectrometry imaging
Thuy Mai Hoang Philipsen
Chalmers, Kemi och kemiteknik, Kemi och biokemi, Fysikalisk kemi
Hoang Philipsen, M., Gu, C., Ewing, A. Imaging mass spectrometry shows that zinc deficiency leads to lipid changes in Drosophila brain similar to cognitive impairing drugs
Interplay between Cocaine, Drug Removal, and Methylphenidate Reversal on Phospholipid Alterations in Drosophila Brain Determined by Imaging Mass Spectrometry
ACS Chemical Neuroscience,; Vol. 11(2020)p. 806-813
Artikel i vetenskaplig tidskrift
Lipids are the building blocks of cellular structures and play an important role in the signal transduction. Imagine the cell is your house and the lipids are the fence around the house. Mails have to pass through the fence to transfer the information back and forth. Hence, lipid changes can result in the aberrant communication among cells that is associated with several diseases, injuries, and disorders. We, therefore, investigate the changes in lipid composition in the brain caused by drugs or diet like cocaine, methylphenidate, omega-3 fatty acids, and dietary zinc deficiency. To do that, I used a mass spectrometry imaging technique to image several different lipid molecules in the fly brain after drug treatment. The technique works like shooting a gun. When the bullets hit the surface, many fragments of materials are blown off. In this technique, an ion beam is used instead of the gun to generate the ionized molecules in a very small area of the brain. The beam is capable of scanning the entire brain to make images of different lipids. Owing to the obtained images, I can determine the alteration of lipids induced by drugs or diet.
Livsvetenskaper och teknik (2010-2018)
Infrastruktur för kemisk avbildning
Lärande och undervisning
Doktorsavhandlingar vid Chalmers tekniska högskola. Ny serie: 4713
Chalmers tekniska högskola
Delaktigheten, CA building
Opponent: Ian Gilmore, Head of Science at the National Physical Laboratory (NPL), UK