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Anal Bioanal Chem. 2018 Oct;410(26):6733-6749. doi: 10.1007/s00216-018-1295-0. Epub 2018 Aug 10.

Longitudinal investigation of the metabolome of 3D aggregating brain cell cultures at different maturation stages by 1H HR-MAS NMR.

Author information

1
Departments of BioMedical Research and Radiology, University of Bern, Erlachstrasse 9a, 3012, Bern, Switzerland.
2
Department of Chemistry and Biochemistry, University of Bern, Freiestrasse 3, 3012, Bern, Switzerland.
3
Department of Physiology, University of Lausanne, Rue du Bugnon 7, 1005, Lausanne, Switzerland.
4
Swiss Center for Applied Human Toxicology (SCAHT), Basel, Switzerland.
5
Departments of BioMedical Research and Radiology, University of Bern, Erlachstrasse 9a, 3012, Bern, Switzerland. peter.vermathen@insel.ch.

Abstract

The aim of the present study was to establish the developmental profile of metabolic changes of 3D aggregating brain cell cultures by 1H high-resolution magic angle spinning (HR-MAS) NMR spectroscopy. The histotypic 3D brain aggregate, containing all brain cell types, is an excellent model for mechanistic studies including OMICS analysis; however, their metabolic profile has not been yet fully investigated. Chemometric analysis revealed a clear separation of samples from the different maturation time points. Metabolite concentration evolutions could be followed and revealed strong and various metabolic alterations. The strong metabolite evolution emphasizes the brain modeling complexity during maturation, possibly reflecting physiological processes of brain tissue development. The small observed intra- and inter-experimental variabilities show the robustness of the combination of 1H-HR-MAS NMR and 3D brain aggregates, making it useful to investigate mechanisms of toxicity that will ultimately contribute to improve predictive neurotoxicology. Graphical Abstract ᅟ.

KEYWORDS:

3D brain cell cultures; Brain aggregates; Chemometrics; High-resolution magic angle spinning; Nuclear magnetic resonance

PMID:
30094790
DOI:
10.1007/s00216-018-1295-0
[Indexed for MEDLINE]

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