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Bergman, Hilde-Marlene
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Publications (8 of 8) Show all publications
Bergman, H.-M., Lindfors, L., Palm, F., Kihlberg, J. & Lanekoff, I. (2019). Metabolite aberrations in early diabetes detected in rat kidney using mass spectrometry imaging. Analytical and Bioanalytical Chemistry, 411(13), 2809-2816
Open this publication in new window or tab >>Metabolite aberrations in early diabetes detected in rat kidney using mass spectrometry imaging
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2019 (English)In: Analytical and Bioanalytical Chemistry, ISSN 1618-2642, E-ISSN 1618-2650, Vol. 411, no 13, p. 2809-2816Article in journal (Refereed) Published
Abstract [en]

Diabetic kidney disease is a serious complication of diabetes that can ultimately lead to end-stage renal disease. The pathogenesis of diabetic kidney disease is complex, and fundamental research is still required to provide a better understanding of the driving forces behind it. We report regional metabolic aberrations from an untargeted mass spectrometry imaging study of kidney tissue using an insulinopenic rat model of diabetes. Diabetes was induced by intravenous injection of streptozotocin, and kidneys were harvested 2weeks thereafter. Imaging was performed using nanospray desorption electrospray ionization connected to a high-mass-resolving mass spectrometer. No histopathological changes were observed in the kidney sections; however, mass spectrometry imaging revealed a significant increase in several 18-carbon unsaturated non-esterified fatty acid species and monoacylglycerols. Notably, these 18-carbon acyl chains were also constituents of several increased diacylglycerol species. In addition, a number of short- and long-chain acylcarnitines were found to be accumulated while several amino acids were depleted. This study presents unique regional metabolic data indicating a dysregulated energy metabolism in renal mitochondria as an early response to streptozotocin-induced type I diabetes.

National Category
Analytical Chemistry
Research subject
Chemistry with specialization in Analytical Chemistry
Identifiers
urn:nbn:se:uu:diva-347672 (URN)10.1007/s00216-019-01721-5 (DOI)000468133600008 ()30895347 (PubMedID)
Funder
Swedish Foundation for Strategic Research Swedish Research CouncilSwedish Diabetes AssociationAstraZeneca
Note

Title in dissertation list of papers: Metabolite aberrations at early onset of diabetes detected in rat kidney using mass spectrometry imaging

Available from: 2018-04-05 Created: 2018-04-05 Last updated: 2020-03-24Bibliographically approved
Bergman, H.-M. (2018). Applications of nanospray desorption electrospray ionization mass spectrometry: In situ lipid and metabolite analysis from cells to tissue. (Doctoral dissertation). Uppsala: Acta Universitatis Upsaliensis
Open this publication in new window or tab >>Applications of nanospray desorption electrospray ionization mass spectrometry: In situ lipid and metabolite analysis from cells to tissue
2018 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Ambient mass spectrometry (MS) has proved to be an important addition to the bioanalytical toolbox. These methods perform analyte sampling and ionization under atmospheric pressure, and require very little sample preparation other than the sampling process in front of the machine. Nanospray desorption electrospray ionization (nano-DESI) is an ambient MS technique developed in 2010 that utilizes localized liquid extraction for surface sampling. The aim of this thesis was to explore the possibilities of this technique, and identify areas in which nano-DESI MS could further contribute to the community of MS-based surface analysis.

One such area was found to be mass spectrometry imaging (MSI) of small-molecule neurotransmitters. By the use of deuterated standards of acetylcholine, γ-aminobutyric acid and glutamate, the respective endogenous compounds were successfully imaged in coronal sections of rat brain. The use of internal standards was shown to be essential to compensatee for matrix effects in different regions of the brain. In a second imaging study, nano-DESI MSI was used to compare the chemical profiles of diabetic rat kidney tissue and control. Analysis was performed on kidney two weeks after diabetic onset, before any pathohistological changes relating to diabetic nephropathy can be seen in a microscope. In our study, it was shown that a large number of chemical species related to energy metabolism were detected with altered signal intensity in diabetic kidney tissue.

To push the limits of nano-DESI analysis, its use for single-cell analysis was evaluated. By placing buccal epithelial cells in contact with the nano-DESI probe, it was possible to identify 46 endogenous compounds and detect differences between cells from three human donors. In addition, it was shown that molecules from single cells on a surface could be detected by scanning the surface with the nano-DESI probe, which opens up for development of an automated analysis with higher throughput.

The last study in this thesis was concerned with method development rather than application, as it presented a setup for pneumatically assisted nano-DESI. Evaluation showed that the setup provided improved sensitivity in the analysis of small metabolites, and provided the possibility of using pure water as nano-DESI solvent.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2018. p. 78
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Science and Technology, ISSN 1651-6214 ; 1660
Keywords
Mass spectrometry, mass spectrometry imaging (MSI), nanospray desorption electrospray ionization (nano-DESI), single-cell analysis, neurotransmitter imaging, diabetic nephropathy, pneumatic nebulization, lipidomics, metabolomics
National Category
Chemical Sciences
Research subject
Chemistry with specialization in Analytical Chemistry
Identifiers
urn:nbn:se:uu:diva-347674 (URN)978-91-513-0307-9 (ISBN)
Public defence
2018-05-25, A1:107a, BMC, Husargatan 3, Uppsala, 13:00 (English)
Opponent
Supervisors
Available from: 2018-05-03 Created: 2018-04-05 Last updated: 2018-10-08
Bergman, H.-M., Duncan, K. D. & Lanekoff, I. (2018). Single‐Cell Mass Spectrometry. In: Editor-in-Chief Robert A. Meyers (Ed.), Encyclopedia of Analytical Chemistry: Applications, Theory and Instrumentation. Wiley-VCH Verlagsgesellschaft
Open this publication in new window or tab >>Single‐Cell Mass Spectrometry
2018 (English)In: Encyclopedia of Analytical Chemistry: Applications, Theory and Instrumentation / [ed] Editor-in-Chief Robert A. Meyers, Wiley-VCH Verlagsgesellschaft, 2018Chapter in book (Refereed)
Abstract [en]

Over the past few decades, the chemical characterization of single cells has improved immensely. In particular, mass spectrometry (MS) has pioneered direct analysis of metabolites, lipids, and peptides from single cells. This progress has been enabled by new and improved strategies for ionization and sampling, where a multitude of techniques for single‐cell MS has contributed unique insights to many different disciplines. Here, an overview of the main three techniques secondary ion mass spectrometry (SIMS), matrix‐assisted laser desorption ionization (MALDI), and ambient ionization for direct single‐cell MS analysis are presented, including some example studies detailing the use of single‐cell MS.

Place, publisher, year, edition, pages
Wiley-VCH Verlagsgesellschaft, 2018
National Category
Analytical Chemistry
Research subject
Chemistry with specialization in Analytical Chemistry
Identifiers
urn:nbn:se:uu:diva-367252 (URN)10.1002/9780470027318.a9580 (DOI)9780470027318 (ISBN)
Available from: 2018-11-29 Created: 2018-11-29 Last updated: 2018-11-30Bibliographically approved
Duncan, K. D., Bergman, H.-M. & Andersson, I. (2017). A pneumatically assisted nanospray desorption electrospray ionization source for increased solvent versatility and enhanced metabolite detection from tissue. The Analyst, 142(18), 3424-3431
Open this publication in new window or tab >>A pneumatically assisted nanospray desorption electrospray ionization source for increased solvent versatility and enhanced metabolite detection from tissue
2017 (English)In: The Analyst, ISSN 0003-2654, E-ISSN 1364-5528, Vol. 142, no 18, p. 3424-3431Article in journal (Refereed) Published
Abstract [en]

Nanospray desorption electrospray ionization (nano-DESI) has been established as a powerful technique for mass spectrometry imaging (MSI) of biomolecules from tissue samples. The direct liquid extraction of analytes from a surface at ambient pressure negates the need for significant sample preparation or matrix application. Although many recent studies have applied nano-DESI to new and exciting applications, there has not been much work in the development and improvement of the nano-DESI source. Here, we incorporate a nebulizer to replace the self-aspirating secondary capillary in the conventional nano-DESI setup, and characterize the device by use of rat kidney tissue sections. We find that the pneumatically assisted nano-DESI device offers improved sensitivity for metabolite species by 1-3 orders of magnitude through more complete desolvation and reduced ionization suppression. Further, the pneumatically assisted nano-DESI device reduces the dependence on probe-to-surface distance and enables sampling and imaging using pure water as the nano-DESI solvent. This provides exclusive detection and imaging of many highly polar endogenous species. Overall, the developed pneumatically assisted nano-DESI device provides more versatile solvent selection and an increased sensitivity for metabolites, which generates ion images of higher contrast - allowing for more intricate studies of metabolite distribution.

Place, publisher, year, edition, pages
ROYAL SOC CHEMISTRY, 2017
National Category
Chemical Sciences
Identifiers
urn:nbn:se:uu:diva-334756 (URN)10.1039/c7an00901a (DOI)000409919200016 ()28828451 (PubMedID)
Funder
Swedish Foundation for Strategic Research , SSF ICA-6Swedish Research Council, VR 621-2013-4231
Available from: 2017-11-27 Created: 2017-11-27 Last updated: 2018-11-29
Bergman, H.-M. & Lanekoff, I. (2017). Profiling and quantifying endogenous molecules in single cells using nano-DESI MS. The Analyst, 142(19), 3639-3647
Open this publication in new window or tab >>Profiling and quantifying endogenous molecules in single cells using nano-DESI MS
2017 (English)In: The Analyst, ISSN 0003-2654, E-ISSN 1364-5528, Vol. 142, no 19, p. 3639-3647Article in journal (Refereed) Published
Abstract [en]

Molecular profiling of single cells has the potential to significantly advance our understanding of cell function and cellular processes of importance to health and disease. In particular, small molecules with rapid turn-over rates can reveal activated metabolic pathways resulting from an altered chemical environment or cellular events such as differentiation. Consequently, techniques for quantitative metabolite detection acquired in a higher throughput manner are needed to characterize the biological variability between seemingly homogenous cells. Here, we show that nanospray desorption electrospray ionization (nano-DESI) mass spectrometry ( MS) enables sensitive molecular profiling and quantification of endogenous species in single cells in a higher throughput manner. Specifically, we show a large number of detected amino acids and phospholipids, including plasmalogens, readily detected from single cheek cells. Further, by incorporating a phosphatidylcholine ( PC) internal standard into the nano-DESI solvent, we determined the total amount of PC in one cell to be 1.2 pmoles. Finally, we describe a higher throughput approach where molecules in single cells are automatically profiled. These developments in single cell analysis provide a basis for future studies to understand cellular processes related to drug effects, cell differentiation and altered chemical microenvironments.

Place, publisher, year, edition, pages
ROYAL SOC CHEMISTRY, 2017
National Category
Analytical Chemistry
Research subject
Chemistry with specialization in Analytical Chemistry
Identifiers
urn:nbn:se:uu:diva-336430 (URN)10.1039/c7an00885f (DOI)000411703800013 ()28835951 (PubMedID)
Funder
Swedish Research Council, VR 621-2013-4231Swedish Foundation for Strategic Research , SSF ICA-6
Available from: 2017-12-15 Created: 2017-12-15 Last updated: 2018-11-29
Bergman, H.-M. (2016). Applications of nanospray desorption electrospray ionization mass spectrome: Analysis of lipids and metabolites in brain tissue sections and single cells. (Licentiate dissertation). Uppsala: Department of Chemistry, Uppsala University
Open this publication in new window or tab >>Applications of nanospray desorption electrospray ionization mass spectrome: Analysis of lipids and metabolites in brain tissue sections and single cells
2016 (English)Licentiate thesis, comprehensive summary (Other academic)
Place, publisher, year, edition, pages
Uppsala: Department of Chemistry, Uppsala University, 2016. p. 37
Keywords
Nano-DESI, single cell analysis, small molecule neurotransmitters, mass spectrometry imaging, MSI, GABA, Glutamate, Acetylcholine
National Category
Analytical Chemistry
Research subject
Chemistry with specialization in Analytical Chemistry
Identifiers
urn:nbn:se:uu:diva-291339 (URN)
Presentation
2016-05-31, B7:113a, Husargatan 3, Uppsala, 10:15 (English)
Opponent
Supervisors
Available from: 2016-11-28 Created: 2016-05-01 Last updated: 2016-11-28Bibliographically approved
Corpeno, R., Dworkin, B., Cacciani, N., Salah, H., Bergman, H.-M., Ravara, B., . . . Larsson, L. (2014). Time-course analysis of mechanical ventilation-induced diaphragm contractile muscle dysfunction in the rat. Journal of Physiology, 592(17), 3859-3880
Open this publication in new window or tab >>Time-course analysis of mechanical ventilation-induced diaphragm contractile muscle dysfunction in the rat
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2014 (English)In: Journal of Physiology, ISSN 0022-3751, E-ISSN 1469-7793, Vol. 592, no 17, p. 3859-3880Article in journal (Refereed) Published
Abstract [en]

Controlled mechanical ventilation (CMV) plays a key role in triggering the impaired diaphragm muscle function and the concomitant delayed weaning from the respirator in critically ill intensive care unit (ICU) patients. To date, experimental and clinical studies have primarily focused on early effects on the diaphragm by CMV, or at specific time points. To improve our understanding of the mechanisms underlying the impaired diaphragm muscle function in response to mechanical ventilation, we have performed time‐resolved analyses between 6 h and 14 days using an experimental rat ICU model allowing detailed studies of the diaphragm in response to long‐term CMV. A rapid and early decline in maximum muscle fibre force and preceding muscle fibre atrophy was observed in the diaphragm in response to CMV, resulting in an 85% reduction in residual diaphragm fibre function after 9–14 days of CMV. A modest loss of contractile proteins was observed and linked to an early activation of the ubiquitin proteasome pathway, myosin:actin ratios were not affected and the transcriptional regulation of myosin isoforms did not show any dramatic changes during the observation period. Furthermore, small angle X‐ray diffraction analyses demonstrate that myosin can bind to actin in an ATP‐dependent manner even after 9–14 days of exposure to CMV. Thus, quantitative changes in muscle fibre size and contractile proteins are not the dominating factors underlying the dramatic decline in diaphragm muscle function in response to CMV, in contrast to earlier observations in limb muscles. The observed early loss of subsarcolemmal neuronal nitric oxide synthase activity, onset of oxidative stress, intracellular lipid accumulation and post‐translational protein modifications strongly argue for significant qualitative changes in contractile proteins causing the severely impaired residual function in diaphragm fibres after long‐term mechanical ventilation. For the first time, the present study demonstrates novel changes in the diaphragm structure/function and underlying mechanisms at the gene, protein and cellular levels in response to CMV at a high temporal resolution ranging from 6 h to 14 days.

National Category
Physiology Neurology
Identifiers
urn:nbn:se:uu:diva-192529 (URN)10.1113/jphysiol.2014.277962 (DOI)000341771400013 ()
Funder
Swedish Research Council, 8651, 4423
Available from: 2013-01-22 Created: 2013-01-22 Last updated: 2018-01-11Bibliographically approved
Bergman, H.-M. & Andersson, I.Detection of endogenous lipids and metabolites in single cells using nano-DESI.
Open this publication in new window or tab >>Detection of endogenous lipids and metabolites in single cells using nano-DESI
(English)Manuscript (preprint) (Other academic)
National Category
Analytical Chemistry
Identifiers
urn:nbn:se:uu:diva-291338 (URN)
Available from: 2016-05-01 Created: 2016-05-01 Last updated: 2018-11-29
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