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Published on: March 15, 2024
Early-life adversity induces metabolic alterations in a rodent model of depression: a differential stress response
Daniël J van Rensburg1, Zander Lindeque2, Ashleigh J Whitney1
1Centre of Excellence for Pharmaceutical Sciences, Faculty of Health Sciences, North-West University (NWU)https://ror.org/010f1sq29, Potchefstroom, South Africa.
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 constructs underlying the pre-pubertal FSL/FRL model.
