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Accepted manuscript

Early-life adversity induces metabolic alterations in a rodent model of depression: a differential stress response perspective

Published online by Cambridge University Press:  05 March 2026

Daniël J van Rensburg ,
Zander Lindeque ,
Ashleigh J Whitney  and
Stephan F Steyn Open the ORCID record for Stephan F Steyn [Opens in a new window]
Daniël J van Rensburg
Affiliation:
Centre of Excellence for Pharmaceutical Sciences, Faculty of Health Sciences, North-West University, Potchefstroom, RSA
Zander Lindeque
Affiliation:
Human Metabolomics, Faculty of Natural and Agricultural Sciences, North-West University, Potchefstroom, RSA
Ashleigh J Whitney
Affiliation:
Centre of Excellence for Pharmaceutical Sciences, Faculty of Health Sciences, North-West University, Potchefstroom, RSA
Stephan F Steyn*
Affiliation:
Centre of Excellence for Pharmaceutical Sciences, Faculty of Health Sciences, North-West University, Potchefstroom, RSA
*
*Corresponding author: Stephan F Steyn, Stephan.steyn@nwu.ac.za
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Abstract

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Objective:

Investigating metabolic differences between pre-pubertal Flinders sensitive (FSL) and resistant (FRL) line rats and determine the impact of early-life adversity on these differences.

Methods:

Untargeted metabolomic profiling of whole-brain tissue from postnatal day 25 Flinders line rats, exposed to maternal separation with early weaning (MSEW), or not, was done by using gas chromatography time-of-flight mass spectrometry (GC-TOF-MS).

Results:

Irrespective of MSEW, FSL rats had higher urea and lower glutamine, norvaline and valine concentrations than age-matched FRL controls. Across strains, MSEW reduced gamma-aminobutyric acid (GABA), glutamate, glutamine, lactate, phenylalanine, norvaline and valine concentrations, whist elevating 2-keto-3-methylbutyric acid, glycerophosphate, and urea. This effect was most pronounced in FRL rats.

Conclusion:

Pre-pubertal FSL rats displayed distinct metabolic signatures associated with altered energy and amino acid metabolism. Early-life stress further disrupts these pathways, highlighting key metabolites as potential targets in the expansion of the biological contracts underlying the pre-pubertal FSL/FRL model.

Keywords

Adverse childhood experiencesDepressive DisorderMetabolomicsRatsStress

Information

Type
Short Communication
Information
Acta Neuropsychiatrica , Accepted manuscript , pp. 1 - 17
Creative Commons
Creative Common License - CCCreative Common License - BY
This is an Open Access article, distributed under the terms of the Creative Commons Attribution licence (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted re-use, distribution and reproduction, provided the original article is properly cited.
Copyright
© The Author(s), 2026. Published by Cambridge University Press on behalf of Scandinavian College of Neuropsychopharmacology