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 i...
| Main Authors: | , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Cambridge University Press
2021-01-01
|
| Series: | QRB Discovery |
| Subjects: | |
| Online Access: | https://www.cambridge.org/core/product/identifier/S2633289221000041/type/journal_article |
| _version_ | 1827994370503081984 |
|---|---|
| author | Elias Ranjbari Mai H. Philipsen Zhaoying Wang Andrew G. Ewing |
| author_facet | Elias Ranjbari Mai H. Philipsen Zhaoying Wang Andrew G. Ewing |
| author_sort | Elias Ranjbari |
| collection | DOAJ |
| description | 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. The SCA results reveal that modafinil slows down the exocytosis process so that, the number of catecholamines released per exocytotic event is enhanced in the modafinil-treated cells. Also, IVIEC results offer an upregulation effect of modafinil on the vesicular catecholamine storage. Mass spectrometry imaging by time-of-flight secondary ion mass spectrometry (ToF-SIMS) illustrates that treatment with modafinil reduces the cylindrical-shaped phosphatidylcholine at the cellular membrane, while the high curvature lipids with conical structures such as phosphatidylethanolamine and phosphatidylinositol are elevated after modafinil treatment. Combining the results obtained by SCA, IVIEC and ToF-SIMS suggests that modafinil-treated cells release a larger portion of their vesicular content at least in part by changing the lipid composition of the cell membrane, suggesting regulation of cognition. |
| first_indexed | 2024-04-10T04:38:52Z |
| format | Article |
| id | doaj.art-b232e3cef26e45d3974bec0df45b760a |
| institution | Directory Open Access Journal |
| issn | 2633-2892 |
| language | English |
| last_indexed | 2024-04-10T04:38:52Z |
| publishDate | 2021-01-01 |
| publisher | Cambridge University Press |
| record_format | Article |
| series | QRB Discovery |
| spelling | doaj.art-b232e3cef26e45d3974bec0df45b760a2023-03-09T12:43:33ZengCambridge University PressQRB Discovery2633-28922021-01-01210.1017/qrd.2021.4Combined electrochemistry and mass spectrometry imaging to interrogate the mechanism of action of modafinil, a cognition-enhancing drug, at the cellular and sub-cellular levelElias Ranjbari0https://orcid.org/0000-0002-7078-7756Mai H. Philipsen1https://orcid.org/0000-0001-6343-4306Zhaoying Wang2https://orcid.org/0000-0002-1620-3385Andrew G. Ewing3https://orcid.org/0000-0002-2084-0133Department of Chemistry and Molecular Biology, University of Gothenburg, Gothenburg, SwedenDepartment of Chemistry and Molecular Biology, University of Gothenburg, Gothenburg, SwedenDepartment of Chemistry and Molecular Biology, University of Gothenburg, Gothenburg, SwedenDepartment of Chemistry and Molecular Biology, University of Gothenburg, Gothenburg, SwedenModafinil 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. The SCA results reveal that modafinil slows down the exocytosis process so that, the number of catecholamines released per exocytotic event is enhanced in the modafinil-treated cells. Also, IVIEC results offer an upregulation effect of modafinil on the vesicular catecholamine storage. Mass spectrometry imaging by time-of-flight secondary ion mass spectrometry (ToF-SIMS) illustrates that treatment with modafinil reduces the cylindrical-shaped phosphatidylcholine at the cellular membrane, while the high curvature lipids with conical structures such as phosphatidylethanolamine and phosphatidylinositol are elevated after modafinil treatment. Combining the results obtained by SCA, IVIEC and ToF-SIMS suggests that modafinil-treated cells release a larger portion of their vesicular content at least in part by changing the lipid composition of the cell membrane, suggesting regulation of cognition.https://www.cambridge.org/core/product/identifier/S2633289221000041/type/journal_articleCognition-enhancing drugmodafinilintracellular vesicle impact electrochemical cytometrysingle-cell amperometrytime-of-flight secondary ion mass spectrometry |
| spellingShingle | Elias Ranjbari Mai H. Philipsen Zhaoying Wang Andrew G. Ewing 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 QRB Discovery Cognition-enhancing drug modafinil intracellular vesicle impact electrochemical cytometry single-cell amperometry time-of-flight secondary ion mass spectrometry |
| title | 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 |
| title_full | 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 |
| title_fullStr | 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 |
| title_full_unstemmed | 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 |
| title_short | 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 |
| title_sort | 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 |
| topic | Cognition-enhancing drug modafinil intracellular vesicle impact electrochemical cytometry single-cell amperometry time-of-flight secondary ion mass spectrometry |
| url | https://www.cambridge.org/core/product/identifier/S2633289221000041/type/journal_article |
| work_keys_str_mv | AT eliasranjbari combinedelectrochemistryandmassspectrometryimagingtointerrogatethemechanismofactionofmodafinilacognitionenhancingdrugatthecellularandsubcellularlevel AT maihphilipsen combinedelectrochemistryandmassspectrometryimagingtointerrogatethemechanismofactionofmodafinilacognitionenhancingdrugatthecellularandsubcellularlevel AT zhaoyingwang combinedelectrochemistryandmassspectrometryimagingtointerrogatethemechanismofactionofmodafinilacognitionenhancingdrugatthecellularandsubcellularlevel AT andrewgewing combinedelectrochemistryandmassspectrometryimagingtointerrogatethemechanismofactionofmodafinilacognitionenhancingdrugatthecellularandsubcellularlevel |