Lipid imaging study provides new knowledge about mechanisms underlying Parkinson's disease

2023-08-23

Through the mapping of lipid molecules within the brain, researchers at Uppsala University are contributing crucial insights into the molecular mechanisms underlying Parkinson's disease. "As the first research team to use MALDI MSI for analysis of lipids in distinct brain regions within an experimental Parkinson’s disease model, we have extracted completely new information," states Ibrahim Kaya at the Faculty of Pharmacy.

The research is carried out at MSI Lab Per Andrén
The research is carried out at MSI Lab Per Andrén

Parkinson's disease is one of the most common neurodegenerative diseases, every year affecting approximately 2,000 people only in Sweden. The disease is caused by the slow death of nerve cells that produce dopamine, but science still lacks sufficient knowledge of the molecular mechanisms behind its development. Several previous studies have underscored the significance of lipids in the process. Now, researchers at Uppsala University's facility for Mass Spectrometry Imaging (MSI) have presented a comprehensive mapping of the relative occurrence and spatial distribution of lipids in the diseased brain.

Ibrahim Kaya, Faculty of Pharmacy
Ibrahim Kaya, Faculty of Pharmacy

“As the first team we have used MALDI-MSI, a technology that generates ultra-high mass resolution, for spatial analysis of lipids in brain tissue samples of an experimental Parkinson’s disease model. By parallel imaging of close to a hundred identified lipids, we have extracted previously unavailable information. Thus, adding another relevant piece to the molecular puzzle of Parkinson’s disease brain research,” says Ibrahim Kaya, researcher at the Department of Pharmaceutical Biosciences and first author of the article published in npj Parkinson's disease.

The results show specific differences in the synthesis, degradation and structure in distribution of lipids in experimental Parkinson's disease when compared to control tissue. These spatial differences of specific sulfatide lipid molecules within disease-related brain regions can affect neuronal functions as well as region-specific lipid metabolism. The research team is currently expanding their investigations with the aim to uncover new insights into the dysregulated lipid metabolism associated with L-DOPA-induced dyskinesia – refering to involuntary and often erratic movements that can develop as a side effect of long-term treatment with L-DOPA, a drug commonly used to manage the motor symptoms of Parkinson's disease.

“Our new publication is achieving good attention and we have high expectations on our next project that we recently started. Biological tissues present highly intricate settings, yet the rapid advancements in MALDI-MSI are unlocking novel scientific opportunities. The demand for the technological capabilities provided by our facility is on the rise. This is particularly pronounced since our integration into SciLifeLab Spatial Omics, a national infrastructure that brings together several leading environments, enhancing our ability to derive even more comprehensive insights from biological samples," says Professor Per Andrén, Professor of Mass Spectrometry Imaging.

FACTS

  • Mass Spectrometry Imaging, MSI, enables analysis and visualisation of endogenous metabolites, neurotransmitters, lipids, peptides and small proteins as well as drugs and their metabolites, in thin biological tissue sections with high molecular specificity.
  • Molecular images are created by ionizing molecules and collecting mass spectra from each position (pixels) on a tissue surface at a selected lateral resolution. Thousands of ions can be detected in each pixel.
  • The distribution of individual molecules on the surface of the tissue section is then extracted and a molecule-specific image is created. The image can be correlated with the original histological image or images produced with other types of imaging methods from the same or consecutive tissue sections.

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CONTACT

KONTAKTa Per AndrénPer Andrén, Professor
Dep. of Pharmaceutical Biosciences
per.andren@farmbio.uu.se

Ibrahim Kaya, forskareIbrahim Kaya, Researcher
Dep. of Pharmaceutical Biosciences
Ibrahim.Kaya@uu.se

text, Magnus Alsne, photo: Mikael Wallerstedt, private

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Last modified: 2024-04-04