Transgenerational transmission of aspartame induced anxiety and changes in glutamate-GABA signaling and gene expression in the amygdala

We show that daily exposure of mice to aspartame, an artificial sweetener found in over 5,000 diet foods and drinks at doses equivalent to only 15% of the FDA recommended maximum daily intake for humans produces anxiety. The anxiety is alleviated by diazepam, a drug used in the treatment of generalized anxiety disorder. We completed RNA sequencing of the amygdala of male mice that were exposed to aspartame or plain drinking water (control), as this brain region regulates anxiety and fear. The aspartame exposure produces changes in the expression of genes regulating excitation-inhibition balance in the amygdala. The anxiety, its response to diazepam and the changes in amygdala gene expression are not limited to the aspartame-exposed individuals but also appear in up to two generations descending from the aspartame-exposed males. Thus, aspartame's neurobehavioral effects are not limited to those who consume it but also impact generations of descendants, a finding that highlights the need for a re-evaluation of current policies on artificial sweetener use. Overall design: Amygdala mRNA from adult C57BL/6 males exposed to either 0.03% aspartame or plain drinking water were analyzed by RNA sequencing of 4 biological replicates using an Illumina NovaSeq 6000