Non-nutritive Sweetener\nAspartame Disrupts Circadian Behavior and Causes Memory Impairment\nin Mice

As\na non-nutritive sweetener, aspartame is widely used\nin everyday life. However, its safety is highly controversial, especially\nits effects on neurobehavior. We evaluated the effects of chronic\ndaily oral administration of aspartame-containing drinking water (at\ndoses equivalent to 7–28% of the FDA-recommended human DIV)\non memory and rhythm behaviors in mice and further investigated changes\nat the molecular level in the brains. Our results demonstrated that\nmice exposed to aspartame exhibited memory impairment. Disorders of\nhippocampal neurotransmitter metabolism and pathological damage may\nbe responsible for the aspartame-induced memory impairment via inhibition\nof the BDNF/TrkB pathway. Furthermore, our findings suggested that\ndisturbed clock gene expression in the hypothalamus after aspartame\nexposure led to altered rest–activity behavior, and this disruption\nof the circadian rhythm may exacerbate memory impairment. This study\nhighlights the negative neurobehavioral effects of aspartame and provides\nvaluable insights into its rational and safe use.