Sažetak sa skupa
https://doi.org/10.21857/ypn4oc4189
Imaging Mass Spectrometry – A Window into the Molecular Diversity of the Brain
Vedrana Ivić
orcid.org/0000-0002-8185-1960
; Department for Medical Biology and Genetics, Faculty of Medicine Osijek, J. J. Strossmayer University of Osijek, J. Huttlera 4, HR-31000 Osijek, Croatia;
Kristina Mlinac-Jerković
orcid.org/0000-0002-4309-5447
; Laboratory for Molecular Neurobiology and Neurochemistry, Croatian Institute for Brain Research, Šalata 12, HR-10000 Zagreb, Croatia;, Department of Chemistry and Biochemistry, School of Medicine, University of Zagreb, Šalata 3, HR-10000 Zagreb, Croatia
Željko Debeljak
orcid.org/0000-0002-1789-5387
; Clinical Institute of Laboratory Diagnostics, Osijek University Hospital Centre, J. Huttlera 4, HR-31000 Osijek, Croatia; Department of Pharmacology, Faculty of Medicine, J. J. Strossmayer University of Osijek, J. Huttlera 4, HR-31000 Osijek, Croatia
Marija Heffer
orcid.org/0000-0001-6770-7359
; Department for Medical Biology and Genetics, Faculty of Medicine Osijek, J. J. Strossmayer University of Osijek, J. Huttlera 4, HR-31000 Osijek, Croatia;
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* Dopisni autor.
Sažetak
The molecular complexity of brain composition underlies its anatomical complexity. The extraction
of molecules from tissue homogenates facilitates molecular analysis but results in a loss of anatomical
organization. By employing histological and multiplex immunohistochemical methods, the histology
of the tissue is preserved, but only a limited number of molecules (1 – 100) can be visualized. Adding
to the limitations of traditional research, histological epitopes are often selected based on hypotheses
that may prove incorrect, leading to longer and more expensive investigations.
To address these challenges, the method of imaging mass spectrometry (IMS) was developed. IMS
maintains the anatomical integrity of the tissue while measuring over a thousand molecular signals.
Depending on tissue processing, the resulting signals can reflect protein composition (proteomics) or
pertain to small metabolites (metabolomics) and lipids (lipidomics). When similar samples of normal
tissue are available, additional statistical analysis helps identify molecules with statistically significant
deviations. Further bioinformatics processing, using existing databases, allows these molecules to be
placed within relevant metabolic processes or to determine transcription factors influencing their
levels.
Unlike studies that begin with a hypothesis, IMS is often hypothesis non-driven or untargeted analysis.
Such analysis aims to eliminate researcher bias and identify relevant pathophysiological mechanisms.
IMS can also be targeted, focusing on just one or a very small set of molecules. This approach can reveal
the distribution of a drug and its metabolites in brain tissue, assess viral neurotropism, or illustrate
the distribution of a toxic metabolite.
In our previous works, we explored both approaches. Using untargeted IMS analysis of the brains
of mice with a knockout gene for GD3 synthase and a deficiency of two (GD1b and GT1b) of the
four main gangliosides, we demonstrated a disruption in the synthesis of ubiquinone, porphyrin, and
long-chain fatty acids. In the study presenting a new method for isolating lipid rafts without the use
of detergents, targeted IMS was employed to demonstrate the loss of all four main glycolipids in the
brain (GM1, GD1a, GD1b, and GT1b) from cerebellar tissue sections after treatment with detergents
Triton X100 and Brij O20.
Whether targeted or untargeted, IMS analysis generate large datasets, accelerate research, and enhance
the utility of rare samples. Combined with other imaging or biochemical methods, IMS is a powerful
tool in translational medicine.
Ključne riječi
imaging mass spectrometry, multiplex methods, gangliosides
Hrčak ID:
333468
URI
Datum izdavanja:
25.6.2025.
Posjeta: 370 *