Analytical and Bioanalytical Chemistry

, Volume 410, Issue 26, pp 6733–6749 | Cite as

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

  • Gaëlle Diserens
  • Martina Vermathen
  • Marie-Gabrielle Zurich
  • Peter VermathenEmail author
Paper in Forefront


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


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



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).

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

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).

Supplementary material

216_2018_1295_MOESM1_ESM.pdf (491 kb)
ESM 1 (PDF 491 kb)


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Departments of BioMedical Research and RadiologyUniversity of BernBernSwitzerland
  2. 2.Department of Chemistry and BiochemistryUniversity of BernBernSwitzerland
  3. 3.Department of PhysiologyUniversity of LausanneLausanneSwitzerland
  4. 4.Swiss Center for Applied Human Toxicology (SCAHT)BaselSwitzerland

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