Chronic Effect of Aspartame on Ionic Homeostasis and Monoamine Neurotransmitters in the Rat Brain

Int J Toxicol. 2014 Jul;33(4):332-341. doi: 10.1177/1091581814537087. Epub 2014 May 28.

Abstract

Aspartame is one of the most widely used artificial sweeteners globally. Data concerning acute neurotoxicity of aspartame is controversial, and knowledge on its chronic effect is limited. In the current study, we investigated the chronic effects of aspartame on ionic homeostasis and regional monoamine neurotransmitter concentrations in the brain. Our results showed that aspartame at high dose caused a disturbance in ionic homeostasis and induced apoptosis in the brain. We also investigated the effects of aspartame on brain regional monoamine synthesis, and the results revealed that there was a significant decrease of dopamine in corpus striatum and cerebral cortex and of serotonin in corpus striatum. Moreover, aspartame treatment significantly alters the tyrosine hydroxylase activity and amino acids levels in the brain. Our data suggest that chronic use of aspartame may affect electrolyte homeostasis and monoamine neurotransmitter synthesis dose dependently, and this might have a possible effect on cognitive functions.

Keywords: Na+-K+-ATPase; apoptosis; aspartame; monoamines; phenylalanine.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • Apoptosis*
  • Aspartame / administration & dosage
  • Aspartame / adverse effects*
  • Cerebral Cortex / enzymology
  • Cerebral Cortex / metabolism*
  • Corpus Striatum / enzymology
  • Corpus Striatum / metabolism*
  • Dopamine Antagonists / administration & dosage
  • Dopamine Antagonists / adverse effects*
  • Male
  • Nerve Tissue Proteins / antagonists & inhibitors
  • Nerve Tissue Proteins / metabolism
  • Neurons / enzymology
  • Neurons / metabolism
  • Neurotoxicity Syndromes / enzymology
  • Neurotoxicity Syndromes / etiology
  • Neurotoxicity Syndromes / metabolism
  • Non-Nutritive Sweeteners / administration & dosage
  • Non-Nutritive Sweeteners / adverse effects*
  • Phenylalanine / agonists
  • Phenylalanine / metabolism
  • Random Allocation
  • Rats, Wistar
  • Serotonin Antagonists / administration & dosage
  • Serotonin Antagonists / adverse effects*
  • Sodium-Potassium-Exchanging ATPase / antagonists & inhibitors
  • Sodium-Potassium-Exchanging ATPase / metabolism
  • Toxicity Tests, Chronic
  • Tryptophan / antagonists & inhibitors
  • Tryptophan / metabolism
  • Tyrosine / agonists
  • Tyrosine / metabolism
  • Tyrosine 3-Monooxygenase / antagonists & inhibitors
  • Tyrosine 3-Monooxygenase / metabolism
  • Water-Electrolyte Imbalance / enzymology
  • Water-Electrolyte Imbalance / etiology
  • Water-Electrolyte Imbalance / metabolism

Substances

  • Dopamine Antagonists
  • Nerve Tissue Proteins
  • Non-Nutritive Sweeteners
  • Serotonin Antagonists
  • Tyrosine
  • Phenylalanine
  • Tryptophan
  • Tyrosine 3-Monooxygenase
  • Sodium-Potassium-Exchanging ATPase
  • Aspartame