Mass spectrometry imaging of free-floating brain sections detects pathological lipid distribution in a mouse model of Alzheimer's-like pathology

Strnad, Štěpán; Pražienková, Veronika; Holubová, Martina; Sýkora, David; Cvačka, Josef; Maletı́nská, Lenka; Železná, Blanka; Kuneš, Jaroslav; Vrkoslav, Vladimír

doi:10.1039/d0an00592d

Cited by 15 publications

(17 citation statements)

References 65 publications

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“…Using rodent brain tissue, which was the most used sample to study neurological diseases, to compare the change of biomolecules in brain tissue by the MSI was a useful approach to identify disease biomarkers. − However, since there are individual differences in biology and the influence of experimental operation, there may be a great difference in the outline and location of brain regions for the brain tissue sections between the experimental group and the control group. In order to reduce these differences, it was necessary to compare them in the same coordinates.…”

Section: Resultsmentioning

confidence: 99%

Automatic Registration of the Mass Spectrometry Imaging Data of Sagittal Brain Slices to the Reference Atlas

Tian

Hou

Zuo

et al. 2021

J. Am. Soc. Mass Spectrom.

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The registration of the mass spectrometry imaging (MSI) data with mouse brain tissue slices from the atlases could perform automatic anatomical interpretation, and the comparison of MSI data in particular brain regions from different mice could be accelerated. However, the current registration of MSI data with mouse brain tissue slices is mainly focused on the coronal. Although the sagittal plane is able to provide more information about brain regions on a single histological slice than the coronal, it is difficult to directly register the complete sagittal brain slices of a mouse as a result of the more significant individualized differences and more positional shifts of brain regions. Herein, by adding the auxiliary line on the two brain regions of central canal (CC) and cerebral peduncle (CP), the registration accuracy of the MSI data with sagittal brain slices has been improved (∼2–5-folds for different brain regions). Moreover, the histological sections with different degrees deformation and different dyeing effects have been used to verify that this pipeline has a certain universality. Our method facilitates the rapid comparison of sagittal plane MSI data from different animals and accelerates the application in the discovery of disease markers.

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Section: Resultsmentioning

confidence: 99%

Automatic Registration of the Mass Spectrometry Imaging Data of Sagittal Brain Slices to the Reference Atlas

Tian

Hou

Zuo

et al. 2021

J. Am. Soc. Mass Spectrom.

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“…MALDI-MSI was used for this purpose. This method has been proven useful for analysis of the distribution of lipids in relation to neurodegenerative processes [ 38 , 39 ]. Spectra acquired in reflector negative ion mode showed consistent differences in lipid content in the grey matter of wt and hyh mice but not in the white matter.…”

Section: Resultsmentioning

confidence: 99%

Identification of key molecular biomarkers involved in reactive and neurodegenerative processes present in inherited congenital hydrocephalus

Ojeda-Pérez

Campos-Sandoval

García-Bonilla

et al. 2021

Fluids Barriers CNS

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Background Periventricular extracellular oedema, myelin damage, inflammation, and glial reactions are common neuropathological events that occur in the brain in congenital hydrocephalus. The periventricular white matter is the most affected region. The present study aimed to identify altered molecular and cellular biomarkers in the neocortex that can function as potential therapeutic targets to both treat and evaluate recovery from these neurodegenerative conditions. The hyh mouse model of hereditary hydrocephalus was used for this purpose. Methods The hyh mouse model of hereditary hydrocephalus (hydrocephalus with hop gait) and control littermates without hydrocephalus were used in the present work. In tissue sections, the ionic content was investigated using energy dispersive X-ray spectroscopy scanning electron microscopy (EDS-SEM). For the lipid analysis, matrix-assisted laser desorption ionization mass spectrometry imaging (MALDI-MSI) was performed in frozen sections. The expression of proteins in the cerebral white matter was analysed by mass spectrometry. The oligodendrocyte progenitor cells (OPCs) were studied with immunofluorescence in cerebral sections and whole-mount preparations of the ventricle walls. Results High sodium and chloride concentrations were found indicating oedema conditions in both the periventricular white matter and extending towards the grey matter. Lipid analysis revealed lower levels of two phosphatidylinositol molecular species in the grey matter, indicating that neural functions were altered in the hydrocephalic mice. In addition, the expression of proteins in the cerebral white matter revealed evident deregulation of the processes of oligodendrocyte differentiation and myelination. Because of the changes in oligodendrocyte differentiation in the white matter, OPCs were also studied. In hydrocephalic mice, OPCs were found to be reactive, overexpressing the NG2 antigen but not giving rise to an increase in mature oligodendrocytes. The higher levels of the NG2 antigen, diacylglycerophosphoserine and possibly transthyretin in the cerebrum of hydrocephalic hyh mice could indicate cell reactions that may have been triggered by inflammation, neurocytotoxic conditions, and ischaemia. Conclusion Our results identify possible biomarkers of hydrocephalus in the cerebral grey and white matter. In the white matter, OPCs could be reacting to acquire a neuroprotective role or as a delay in the oligodendrocyte maturation.

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“…In recent years, MSI has widely been used for lipidomics for detecting possible biomarkers in brain, liver, oral, breast, colorectal, skin, or other cancers [ 2 , 20 , 76 ]; in brain and neuronal tissue research [ 77 ] and models of fetal or adult cerebral ischemia [ 19 , 78 , 79 , 80 ]; in neurodegenerative disorders [ 81 ] such as Alzheimer’s disease [ 82 ] or Niemann-Pick disease [ 83 ]; as well as in cardiovascular diseases [ 84 ] such as atherosclerosis.…”

Section: Discussionmentioning

confidence: 99%

Lipid Changes in the Peri-Implantation Period with Mass Spectrometry Imaging: A Systematic Review

Gitta

Márk

Szentpéteri

et al. 2023

Life

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Mass spectrometry imaging is a sensitive method for detecting molecules in tissues in their native form. Lipids mainly act as energy stores and membrane constituents, but they also play a role in lipid signaling. Previous studies have suggested an important role of lipids in implantation; therefore, our aim was to investigate the lipid changes during this period based on the available literature. The systematic literature search was performed on Ovid MEDLINE, Cochrane Library, Embase, and LILACS. We included studies about lipid changes in the early embryonal stage of healthy mammalian development published as mass spectrometry imaging. The search retrieved 917 articles without duplicates, and five articles were included in the narrative synthesis of the results. Two articles found a different spatial distribution of lipids in the early bovine embryo and receptive uterus. Three articles investigated lipids in mice in the peri-implantation period and found a different spatial distribution of several glycerophospholipids in both embryonic and maternal tissues. Although only five studies from three different research groups were included in this systematic review, it is clear that the spatial distribution of lipids is diverse in different tissues and their distribution varies from day to day. This may be a key factor in successful implantation, but further studies are needed to elucidate the exact mechanism.

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Mass spectrometry imaging of free-floating brain sections detects pathological lipid distribution in a mouse model of Alzheimer's-like pathology

Abstract: The applicability of paraformaldehyde-fixed free-floating sections for the MALDI MSI of lipids was studied and the developed procedure was used for studying lipid changes in a mouse model of Alzheimer's pathology.

Cited by 15 publications

References 65 publications

Automatic Registration of the Mass Spectrometry Imaging Data of Sagittal Brain Slices to the Reference Atlas

Automatic Registration of the Mass Spectrometry Imaging Data of Sagittal Brain Slices to the Reference Atlas

Identification of key molecular biomarkers involved in reactive and neurodegenerative processes present in inherited congenital hydrocephalus

Lipid Changes in the Peri-Implantation Period with Mass Spectrometry Imaging: A Systematic Review

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