| 1. |
- Gu, Chaoyi, 1992, et al.
(författare)
-
Omega-3 and-6 Fatty Acids Alter the Membrane Lipid Composition and Vesicle Size to Regulate Exocytosis and Storage of Catecholamines
- 2024
-
Ingår i: ACS CHEMICAL NEUROSCIENCE. - 1948-7193. ; 15:4, s. 816-826
-
Tidskriftsartikel (refereegranskat)abstract
- 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. Incubation of either of the two fatty acids reduces the size of secretory vesicles and enables the incorporation of more double bonds into the cell membrane structure, resulting in higher membrane flexibility. This subsequently affects proteins regulating the dynamics of the exocytotic fusion pore and thereby affects exocytosis. Our data suggest a possible pathway whereby the two essential fatty acids affect the membrane structure to impact exocytosis and provide a potential treatment for diseases and impairments related to catecholamine signaling.
|
|
| 2. |
|
|
| 3. |
- Philipsen, Mai H., 1988, et al.
(författare)
-
Mass Spectrometry Imaging Shows Cocaine and Methylphenidate Have Opposite Effects on Major Lipids in Drosophila Brain
- 2018
-
Ingår i: Acs Chemical Neuroscience. - : American Chemical Society (ACS). - 1948-7193. ; 9:6, s. 1462-1468
-
Tidskriftsartikel (refereegranskat)abstract
- 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 similar to 3 mu m, 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. Principal components image analysis revealed that changes occurred mainly for phosphatidylcholines, phosphatidylethanolamines, and phosphatidylinositols. When the lipid changes caused by cocaine were compared with those induced by methylphenidate, it was shown that these drugs exert opposite effects on the brain lipid structure. We speculate that this might relate to the molecular mechanism of cognition and memory.
|
|
| 4. |
- Philipsen, Mai H., 1988, et al.
(författare)
-
Mass Spectrometry Imaging Shows Modafinil, A Student Study Drug, Changes the Lipid Composition of the Fly Brain
- 2021
-
Ingår i: Angewandte Chemie-International Edition. - : Wiley. - 1433-7851 .- 1521-3773. ; 60:32, s. 17378-17382
-
Tidskriftsartikel (refereegranskat)abstract
- 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. The alteration of brain lipids caused by modafinil is consistent with previous studies about cognition-related drugs and offers a plausible mechanism regarding the action of modafinil in the brain as well as a potential target for the treatment of certain disorders.
|
|
| 5. |
- Philipsen, Mai H., 1988, et al.
(författare)
-
Relative quantification of deuterated omega-3 and-6 fatty acids and their lipid turnover in PC12 cell membranes using TOF-SIMS
- 2018
-
Ingår i: Journal of Lipid Research. - 0022-2275 .- 1539-7262. ; 59:11, s. 2098-2107
-
Tidskriftsartikel (refereegranskat)abstract
- 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 mu M alpha-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. Because of its high spatial resolution, TOF-SIMS can be used to simultaneously provide both chemical information and distribution of various molecules in the sample surface down to the subcellular scale. Data obtained from this analysis of isotopes in the cell samples were used to calculate the relative amounts of long-chain PUFAs and phospholipids from their precursors, alpha-linolenic acid and linoleic acid. Our results show that the FA treatments induced an increase in the amounts of alpha-linolenic acid and linoleic acid and their long-chain conversion products. Moreover, an enhanced level of phospholipid turnover of these FAs in lipids such as phosphatidylcholines, phosphatidylethanolamines, and phosphatidylinositols was also observed in the cell plasma membrane.
|
|
| 6. |
- Ranjbari, Elias, et al.
(författare)
-
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
- 2021
-
Ingår i: QRB Discovery. - : Cambridge University Press (CUP). - 2633-2892. ; 2
-
Tidskriftsartikel (refereegranskat)abstract
- (A) Microscope view during the intracellular vesicle impact electrochemical cytometry experiment (scale bar = 20 μm). (B) Normalised frequency histogram for the number of molecules stored in vesicles in control (blue) and modafinil-Treated cells (red). The distribution fits are shown for control cells with a dashed line and modafinil-Treated cells with a solid line. (C) Average of the number of molecules stored per vesicle in PC12 cells treated without (control) or with 10 μM modafinil. Number of analysed cells: control cells (15 cells) and modafinil-Treated cells (18 cells). The results were compared by a two-Tailed Mann-Whitney rank-sum test,*p < 0.05, p < 0.01 and***p < 0.001. ©
|
|
