Neurometabolic effects of sweetened solution intake during adolescence related to depressive-like phenotype in rats.

Abstract

Objective: Exposure to artificial sweeteners, such as aspartame, during childhood and adolescence has been increasing in recent years. However, the safe use of aspartame has been questioned owing to its potentially harmful effects on the developing brain. The aim of this study was to test whether the chronic consumption

of aspartame during adolescence leads to a depressive-like phenotype and to investigate the possible mecha- nisms underlying these behavioral changes.

Methods: Adolescent male and female rats were given unlimited access to either water, solutions of aspar- tame, or sucrose in their home cages from postnatal day 21 to 55.

Results: Forced swim test revealed that both chronic aspartame and sucrose intake induced depressive-like behaviord, which was more pronounced in males. Additionally, repeated aspartame intake was associated with increased cerebrospinal fluid (CSF) aspartate levels, decreased hippocampal neurogenesis, and reduced activation of the hippocampal leptin signaling pathways in males. In females, we observed a main

effect of aspartame: reducing PI3K/AKT one of the brain-derived neurotrophic factor pathways; aspar- tame also increased CSF aspartate levels and decreased the immunocontent of the GluN2A subunit of

the N-methyl-D-aspartic acid receptor. Conclusion: The findings revealed that repeated aspartame intake during adolescence is associated with a depressive-like phenotype and changes in brain plasticity. Interestingly, males appear to be more vulnerable to the adverse neurometabolic effects of aspartame than females, demonstrating a sexually dimorphic