Sex-comparative study of mouse cerebellum physiology under adult-onset hypothyroidism: The significance of GC-MS metabolomic data normalization in meta-analysis.

Autor: Maga-Nteve C; Metabolic Engineering and Systems Biology Laboratory, Institute of Chemical Engineering Sciences, Foundation for Research and Technology-Hellas (FORTH/ICE-HT), Patras, Greece; School of Medicine, University of Patras, Greece., Vasilopoulou CG; Metabolic Engineering and Systems Biology Laboratory, Institute of Chemical Engineering Sciences, Foundation for Research and Technology-Hellas (FORTH/ICE-HT), Patras, Greece; Human & Animal Physiology Laboratory, Department of Biology, University of Patras, Greece., Constantinou C; Metabolic Engineering and Systems Biology Laboratory, Institute of Chemical Engineering Sciences, Foundation for Research and Technology-Hellas (FORTH/ICE-HT), Patras, Greece., Margarity M; Human & Animal Physiology Laboratory, Department of Biology, University of Patras, Greece., Klapa MI; Metabolic Engineering and Systems Biology Laboratory, Institute of Chemical Engineering Sciences, Foundation for Research and Technology-Hellas (FORTH/ICE-HT), Patras, Greece; Departments of Chemical & Biomolecular Engineering and Bioengineering, University of Maryland, College Park, MD 20742, USA. Electronic address: mklapa@iceht.forth.gr.
Jazyk: angličtina
Zdroj: Journal of chromatography. B, Analytical technologies in the biomedical and life sciences [J Chromatogr B Analyt Technol Biomed Life Sci] 2017 Jan 15; Vol. 1041-1042, pp. 158-166. Date of Electronic Publication: 2016 Dec 12.
DOI: 10.1016/j.jchromb.2016.12.016
Abstrakt: A systematic data quality validation and normalization strategy is an important component of the omic profile meta-analysis, ensuring comparability of the profiles and exclusion of experimental biases from the derived biological conclusions. In this study, we present the normalization methodology applied on the sets of cerebellum gas chromatography-mass spectrometry metabolic profiles of 124days old male and female animals in an adult-onset-hypothyroidism (AOH) mouse model before combining them into a sex-comparative analysis. The employed AOH model concerns the monitoring of the brain physiology of Balb/cJ mice after eight-week administration of 1%w/v KClO 4 in the drinking water, initiated on the 60th day of their life. While originating from the same animal study, the tissues of the two sexes were processed and their profiles acquired and analyzed at different time periods. Hence, the previously published profile set of male mice was first re-annotated based on the presently available resources. Then, after being validated as acquired under the same analytical conditions, both profiles sets were corrected for derivatization biases and filtered for low-confidence measurements based on the same criteria. The final normalized 73-metabolite profiles contribute to the currently few available omic datasets of the AOH effect on brain molecular physiology, especially with respect to sex differentiation. Multivariate statistical analysis indicated one (unknown) and three (succinate, benzoate, myristate) metabolites with significantly higher and lower, respectively, cerebellum concentration in the hypothyroid compared to the euthyroid female mice. The respective numbers for the males were two and 24. Comparison of the euthyroid cerebellum metabolic profiles between the two sexes indicated 36 metabolites, including glucose, myo- and scyllo-inositol, with significantly lower concentration in the females versus the males. This implies that the female mouse cerebellum has been conditioned to smaller changes in its metabolic activity with respect to the pathways involving these metabolites compared to the male animals. In conclusion, our study indicated a much subtler AOH effect on the cerebellum metabolic activity of the female compared to the male mice. The leaner metabolic profile of the female mouse cerebellum was suggested as a potential factor contributing to this phenomenon.
(Copyright © 2016 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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