| 1. |
- Gu, Chaoyi, 1992, et al.
(författare)
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Mass spectrometric imaging of plasma membrane lipid alteration correlated with amperometrically measured activity-dependent plasticity in exocytosis
- 2020
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Ingår i: International Journal of Molecular Sciences. - : MDPI AG. - 1661-6596 .- 1422-0067. ; 21:24, s. 1-10
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Tidskriftsartikel (refereegranskat)abstract
- 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. The lipid changes observed following repetitive stimuli are similar to those after exposure to the cognitive enhancing drug, methylphenidate, examined in a previous study, and offer an interesting point of view regarding the link between plasticity and memory and cognition.
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| 2. |
- Hagvall, Lina, 1978, et al.
(författare)
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Skin permeation studies of chromium species-Evaluation of a reconstructed human epidermis model
- 2023
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Ingår i: Toxicology in Vitro. - 0887-2333 .- 1879-3177. ; 91
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Tidskriftsartikel (refereegranskat)abstract
- A reconstructed human epidermis (RHE) model, the EpiDerm, was investigated and compared to human skin ex vivo regarding tissue penetration and distribution of two chromium species, relevant in both occupational and general exposure in the population. Imaging mass spectrometry was used in analysis of the sectioned tissue. The RHE model gave similar results compared to human skin ex vivo for skin penetration of CrVI. However, the penetration of CrIII into the tissue of the RHE model compared to human skin ex vivo differed markedly, such that in the RHE model the CrIII species accumulated in the tissue layer corresponding to stratum corneum whereas in human skin ex vivo, the CrIII species penetrated evenly through the skin tissue. Further, skin lipids such as cholesterol were less abundant in the RHE model compared to the human skin tissue. Results presented here indicate that the RHE models do not possess the same fundamental properties as human skin tissue. As the RHE models appear to be able to give false negative results, experiments using RHE models for the study of skin penetration should be evaluated with caution.
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| 3. |
- Hoang Philipsen, Thuy Mai, 1988, et al.
(författare)
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Interplay between Cocaine, Drug Removal, and Methylphenidate Reversal on Phospholipid Alterations in Drosophila Brain Determined by Imaging Mass Spectrometry
- 2020
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Ingår i: ACS Chemical Neuroscience. - : American Chemical Society (ACS). - 1948-7193. ; 11:5, s. 806-813
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Tidskriftsartikel (refereegranskat)abstract
- 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, Drosophila melanogaster. 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. Time of flight secondary ion mass spectrometry with a (CO2)6000+ gas cluster ion beam was used to detect intact phospholipids. We show that cocaine has persistent effects, both increasing and decreasing the levels of specific phosphatidylethanolamines and phosphatidylinositols. These changes remain after cocaine withdrawal and are not rescued by methylphenidate. Cocaine is again shown to generally increase the levels of phosphatidylcholines in the fly brain; however, after drug withdrawal, the abundance of these lipids returns to the original level and methylphenidate treatment of the flies following cocaine exposure enhances the reversal of the lipid level reducing them below the original control. The study provides insight into the molecular effects of cocaine and methylphenidate on brain lipids. We suggest that phosphatidylcholines could be a potential target for the treatment of cocaine abuse as well as be a significant hallmark of cognition and memory loss with cocaine.
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| 4. |
- Hoang Philipsen, Thuy Mai, 1988
(författare)
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Interrogation of drug effects on the lipid composition of single cells and Drosophila brain using ToF-SIMS imaging
- 2020
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Lipids are essential for all living organisms on Earth. The most important function of lipids is that they act as the building blocks of cellular membranes. Lipids consist of polar head groups and non-polar tail groups and assemble into bilayer structures to create cell and organelle membranes. The plasma membrane of a cell provides a barrier which segregates cellular internal constituents from the external environment. In addition to acting as a barrier, membrane lipids are involved in many cellular processes including membrane trafficking, signal transduction, fission and fusion. Therefore, various conditions in the central nervous system involving lipid deficiencies can lead to function deficit. There are several drugs that induce the dysregulation of lipid metabolism linked to the impairment or enhancement of cognitive function. Hence, I have studied the lipid alterations in brain induced by drugs with regards to their effects on cognitive processes: cognitive impairing drugs (cocaine and zinc deficiency) and cognitive enhancing drugs (methylphenidate and fatty acids). Much work has been done to investigate the link between lipid metabolisms and these drugs. A powerful technique for lipid analysis is mass spectrometry imaging (MSI). MSI is a surface sensitive method which enables label-free detection of molecules in complex biological systems. In addition, MSI provides the relative composition as well as allows imaging of intact species with high spatial resolution in single experiments. One of the most common MSI techniques is time-of-flight secondary ion mass spectrometry (ToF-SIMS), which achieves high spatial resolution using a focused ion beam to eject and ionize molecules in the sample surface. Recently, gas cluster ion beams have been introduced to reduce the chemical damage during sampling of surfaces and to achieve enhancement of lipid signals. In our studies, ToF-SIMS has been applied to lipids in the membranes of cells and Drosophila melanogaster brain to get a better understanding about the effect of drugs in lipid mechanisms related to neuronal signal transmission. 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.
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| 5. |
- Hoang Philipsen, Thuy Mai, 1988, et al.
(författare)
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Zinc Deficiency Leads to Lipid Changes in Drosophila Brain Similar to Cognitive-Impairing Drugs: An Imaging Mass Spectrometry Study
- 2020
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Ingår i: Chembiochem. - : Wiley. - 1439-4227 .- 1439-7633. ; 21:19, s. 2755-2758
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Tidskriftsartikel (refereegranskat)abstract
- 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 ofDrosophila melanogasterby 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. In contrast, the abundance of phosphatidylethanolamine in the brains of the zinc-deficient flies is lower. These data are consistent with that of cognitive-diminishing drugs, thus providing insight into the biological and molecular effects of zinc deficiency on the major brain lipids and opening a new treatment target for cognitive deficit in zinc deficiency.
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| 6. |
- Majdi, Soodabeh, 1980, et al.
(författare)
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Electrochemistry in and of the Fly Brain
- 2018
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Ingår i: Electroanalysis. - : Wiley. - 1040-0397 .- 1521-4109. ; 30:6, s. 999-1010
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Tidskriftsartikel (refereegranskat)abstract
- Studying brain function and neuronal communication has been always crucial due to the complexity of these systems. A great deal of technology and model systems have been developed to study this subject. Yet, very small invertebrate systems such as the fruit fly, Drosophila are excellent models and often have better defined and more easily manipulated genetics. This review focuses on invivo, ex vivo, and invitro measurements of biogenic amines by electrochemical techniques on the fly nervous system. The methods include capillary electrophoresis, fast scan cyclic voltammetry, and chronoamperometry have been used to study both larval and adult central nervous systems. Better understanding of brain function in model systems should aid in finding solutions to biological and bioanalytical challenges related to human brain function and also neurodegenerative disease.
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| 7. |
- Nguyen, Tho D. K., et al.
(författare)
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Visualization of Partial Exocytotic Content Release and Chemical Transport into Nanovesicles in Cells
- 2022
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Ingår i: Acs Nano. - : American Chemical Society (ACS). - 1936-0851 .- 1936-086X. ; 16:3, s. 4831-4842
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Tidskriftsartikel (refereegranskat)abstract
- For decades, "all-or-none"and "kiss-and-run"were thought to be the only major exocytotic release modes in cell-to-cell communication, while the significance of partial release has not yet been widely recognized and accepted owing to the lack of direct evidence for exocytotic partial release. Correlative imaging with transmission electron microscopy and NanoSIMS imaging and a dual stable isotope labeling approach was used to study the cargo status of vesicles before and after exocytosis; demonstrating a measurable loss of transmitter in individual vesicles following stimulation due to partial release. Model secretory cells were incubated with 13C-labeled l-3,4-dihydroxyphenylalanine, resulting in the loading of 13C-labeled dopamine into their vesicles. A second label, di-N-desethylamiodarone, having the stable isotope 127I, was introduced during stimulation. A significant drop in the level of 13C-labeled dopamine and a reduction in vesicle size, with an increasing level of 127I-, was observed in vesicles of stimulated cells. Colocalization of 13C and 127I- in several vesicles was observed after stimulation. Thus, chemical visualization shows transient opening of vesicles to the exterior of the cell without full release the dopamine cargo. We present a direct calculation for the fraction of neurotransmitter release from combined imaging data. The average vesicular release is 60% of the total catecholamine. An important observation is that extracellular molecules can be introduced to cells during the partial exocytotic release process. This nonendocytic transport process appears to be a general route of entry that might be exploited pharmacologically. © 2022 The Authors. Published by American Chemical Society.
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