Aspartame Causes Developmental Defects and Teratogenicity in Zebra Fish Embryo: Role of Impaired SIRT1/FOXO3a Axis in Neuron Cells

Athiram Pandaram, Jeyakumari Paul, Wankupar Wankhar, Abhimanyu Thakur*, Sakshi Verma, Karthick Vasudevan, Dapkupar Wankhar, Ananth Kumar Kammala, Priyanshu Sharma, Ravindran Jaganathan, Ashok Iyaswamy*, Ravindran Rajan*

*Corresponding author for this work

Research output: Contribution to journalJournal articlepeer-review

1 Citation (Scopus)


Aspartame, a widely used artificial sweetener, is present in many food products and beverages worldwide. It has been linked to potential neurotoxicity and developmental defects. However, its teratogenic effect on embryonic development and the underlying potential mechanisms need to be elucidated. We investigated the concentration- and time-dependent effects of aspartame on zebrafish development and teratogenicity. We focused on the role of sirtuin 1 (SIRT1) and Forkhead-box transcription factor (FOXO), two proteins that play key roles in neurodevelopment. It was found that aspartame exposure reduced the formation of larvae and the development of cartilage in zebrafish. It also delayed post-fertilization development by altering the head length and locomotor behavior of zebrafish. RNA-sequencing-based DEG analysis showed that SIRT1 and FOXO3a are involved in neurodevelopment. In silico and in vitro analyses showed that aspartame could target and reduce the expression of SIRT1 and FOXO3a proteins in neuron cells. Additionally, aspartame triggered the reduction of autophagy flux by inhibiting the nuclear translocation of SIRT1 in neuronal cells. The findings suggest that aspartame can cause developmental defects and teratogenicity in zebrafish embryos and reduce autophagy by impairing the SIRT1/FOXO3a axis in neuron cells.

Original languageEnglish
Article number855
Number of pages19
Issue number4
Publication statusPublished - Apr 2024

Scopus Subject Areas

  • Medicine (miscellaneous)
  • Biochemistry, Genetics and Molecular Biology(all)

User-Defined Keywords

  • aspartame
  • neurodevelopment
  • SIRT1/FOXO3a axis
  • teratogenicity
  • zebrafish embryos


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