scholarly journals Visualising Cholesterol in Brain by On-Tissue Derivatisation and Quantitative Mass Spectrometry Imaging

2020 ◽  
Author(s):  
Roberto Angelini ◽  
Eylan Yutuc ◽  
Mark F Wyatt ◽  
Jillian Newton ◽  
Fowzi Adam Yusuf ◽  
...  

SummaryDespite being a critical molecule for neurobiology and brain health, mass spectrometry imaging (MSI) of cholesterol has been under reported compared to other lipids, due to the difficulty in ionising the sterol molecule. In the present work we have employed an on-tissue enzyme-assisted derivatisation strategy to improve detection of cholesterol in brain tissue sections. We report distribution and levels of cholesterol across specific brain structures of the mouse brain, in a model of Niemann-Pick type C1 (NPC1) disease, and during brain development. MSI revealed how cholesterol changes during development and that in the adult is highest in pons and medulla of the brain stem. Cholesterol was significantly reduced in the corpus callosum and other brain regions in the Npc1 null mouse, confirming hypomyelination at the molecular level. Our study demonstrates the potential of MSI to the study of sterols in neuroscience.

The Analyst ◽  
2016 ◽  
Vol 141 (12) ◽  
pp. 3686-3695 ◽  
Author(s):  
Hilde-Marléne Bergman ◽  
Erik Lundin ◽  
Malin Andersson ◽  
Ingela Lanekoff

Nano-DESI mass spectrometry imaging enables quantitative imaging of small-molecule neurotransmitters which are essential to the function of the nervous system.


2021 ◽  
Vol 7 (2) ◽  
pp. eabe5948
Author(s):  
Elva Fridjonsdottir ◽  
Reza Shariatgorji ◽  
Anna Nilsson ◽  
Theodosia Vallianatou ◽  
Luke R. Odell ◽  
...  

l-DOPA treatment for Parkinson’s disease frequently leads to dyskinesias, the pathophysiology of which is poorly understood. We used MALDI-MSI to map the distribution of l-DOPA and monoaminergic pathways in brains of dyskinetic and nondyskinetic primates. We report elevated levels of l-DOPA, and its metabolite 3-O-methyldopa, in all measured brain regions of dyskinetic animals and increases in dopamine and metabolites in all regions analyzed except the striatum. In dyskinesia, dopamine levels correlated well with l-DOPA levels in extrastriatal regions, such as hippocampus, amygdala, bed nucleus of the stria terminalis, and cortical areas, but not in the striatum. Our results demonstrate that l-DOPA–induced dyskinesia is linked to a dysregulation of l-DOPA metabolism throughout the brain. The inability of extrastriatal brain areas to regulate the formation of dopamine during l-DOPA treatment introduces the potential of dopamine or even l-DOPA itself to modulate neuronal signaling widely across the brain, resulting in unwanted side effects.


Author(s):  
Roberto Angelini ◽  
Eylan Yutuc ◽  
Mark F. Wyatt ◽  
Jillian Newton ◽  
Fowzi A. Yusuf ◽  
...  

The Analyst ◽  
2018 ◽  
Vol 143 (3) ◽  
pp. 654-661 ◽  
Author(s):  
Milad Nazari ◽  
Mark T. Bokhart ◽  
Philip L. Loziuk ◽  
David C. Muddiman

IR-MALDESI quantitative mass spectrometry imaging of glutathione in healthy and cancerous hen ovarian tissues.


2021 ◽  
Vol 15 ◽  
Author(s):  
Md. Mahmudul Hasan ◽  
Mst. Afsana Mimi ◽  
Md. Al Mamun ◽  
Ariful Islam ◽  
A. S. M. Waliullah ◽  
...  

Glycans are diverse structured biomolecules that play crucial roles in various biological processes. Glycosylation, an enzymatic system through which various glycans are bound to proteins and lipids, is the most common and functionally crucial post-translational modification process. It is known to be associated with brain development, signal transduction, molecular trafficking, neurodegenerative disorders, psychopathologies, and brain cancers. Glycans in glycoproteins and glycolipids expressed in brain cells are involved in neuronal development, biological processes, and central nervous system maintenance. The composition and expression of glycans are known to change during those physiological processes. Therefore, imaging of glycans and the glycoconjugates in the brain regions has become a “hot” topic nowadays. Imaging techniques using lectins, antibodies, and chemical reporters are traditionally used for glycan detection. However, those techniques offer limited glycome detection. Mass spectrometry imaging (MSI) is an evolving field that combines mass spectrometry with histology allowing spatial and label-free visualization of molecules in the brain. In the last decades, several studies have employed MSI for glycome imaging in brain tissues. The current state of MSI uses on-tissue enzymatic digestion or chemical reaction to facilitate successful glycome imaging. Here, we reviewed the available literature that applied MSI techniques for glycome visualization and characterization in the brain. We also described the general methodologies for glycome MSI and discussed its potential use in the three-dimensional MSI in the brain.


2021 ◽  
Author(s):  
Jens Habenstein ◽  
Franziska Schmitt ◽  
Sander Liessem ◽  
Alice Ly ◽  
Dennis Trede ◽  
...  

2015 ◽  
Vol 21 (2) ◽  
pp. 187-193 ◽  
Author(s):  
Richard J. A. Goodwin ◽  
Anna Nilsson ◽  
C. Logan Mackay ◽  
John G. Swales ◽  
Maria K. Johansson ◽  
...  

Mass spectrometry imaging (MSI) provides pharmaceutical researchers with a suite of technologies to screen and assess compound distributions and relative abundances directly from tissue sections and offer insight into drug discovery–applicable queries such as blood-brain barrier access, tumor penetration/retention, and compound toxicity related to drug retention in specific organs/cell types. Label-free MSI offers advantages over label-based assays, such as quantitative whole-body autoradiography (QWBA), in the ability to simultaneously differentiate and monitor both drug and drug metabolites. Such discrimination is not possible by label-based assays if a drug metabolite still contains the radiolabel. Here, we present data exemplifying the advantages of MSI analysis. Data of the distribution of AZD2820, a therapeutic cyclic peptide, are related to corresponding QWBA data. Distribution of AZD2820 and two metabolites is achieved by MSI, which [14C]AZD2820 QWBA fails to differentiate. Furthermore, the high mass-resolving power of Fourier transform ion cyclotron resonance MS is used to separate closely associated ions.


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