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

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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.

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Acknowledgements

This work was supported by the UniBE ID-Grant (PV), Swiss National Science Foundation SNF grant no. 200021_14438 (MV), and Swiss Centre for Applied Human Toxicology (SCAHT) grant (MGZ).

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Author notes

  1. Marie-Gabrielle Zurich and Peter Vermathen contributed equally to this work.

Authors and Affiliations

  1. Departments of BioMedical Research and Radiology, University of Bern, Erlachstrasse 9a, 3012, Bern, Switzerland

    Gaëlle Diserens & Peter Vermathen

  2. Department of Chemistry and Biochemistry, University of Bern, Freiestrasse 3, 3012, Bern, Switzerland

    Martina Vermathen

  3. Department of Physiology, University of Lausanne, Rue du Bugnon 7, 1005, Lausanne, Switzerland

    Marie-Gabrielle Zurich

  4. Swiss Center for Applied Human Toxicology (SCAHT), Basel, Switzerland

    Marie-Gabrielle Zurich

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  1. Gaëlle Diserens
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  2. Martina Vermathen
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  3. Marie-Gabrielle Zurich
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  4. Peter Vermathen
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Correspondence to Peter Vermathen.

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Ethical approval was obtained from the VD Service de la consommation et des affaires vétérinaires (authorization number VD3128). Animals were housed and handled following the guidelines of the Ethics Committee for Animal Experimentation of the Swiss Academy of Medical Sciences (SAMS) and the Swiss Academy of Sciences (SCNAT).

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Diserens, G., Vermathen, M., Zurich, MG. et al. Longitudinal investigation of the metabolome of 3D aggregating brain cell cultures at different maturation stages by 1H HR-MAS NMR. Anal Bioanal Chem 410, 6733–6749 (2018). https://doi.org/10.1007/s00216-018-1295-0

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