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 mechanisms underlying these behavioral changes. METHODS: Adolescent male and female rats were given unlimited access to either water, solutions of aspartame, 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; aspartame 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 response. The present results highlighted the importance of understanding the effects caused by the constant use of this artificial sweetener in sensitive periods of development and contribute to regulation of its safe use.