Spatial Learning and Memory Impairment in Growing Mice Induced by Major Oxidized Tyrosine Product Dityrosine

J Agric Food Chem. 2019 Aug 14;67(32):9039-9049. doi: 10.1021/acs.jafc.9b04253. Epub 2019 Aug 6.

Abstract

This study focused on the effects of oxidized tyrosine products (OTPs) and major component dityrosine (DT) on the brain and behavior of growing mice. Male and female mice were treated with daily intragastric administration of either tyrosine (Tyr; 420 μg/kg body weight), DT (420 μg/kg body weight), or OTPs (1909 μg/kg body weight) for 35 days. We found that pure DT and OTPs caused redox state imbalance, elevated levels of inflammatory factors, hippocampal oxidative damage, and neurotransmitter disorders while activating the mitochondrial apoptosis pathway in the hippocampus and downregulating the genes associated with learning and memory. These events eventually led to growing mice learning and memory impairment, lagging responses, and anxiety-like behaviors. Furthermore, the male mice exhibited slightly more oxidative damage than the females. These findings imply that contemporary diets and food-processing strategies of the modern world should be modified to reduce oxidized protein intake.

Keywords: apoptosis; dityrosine; oxidative stress; protein oxidation; spatial learning and memory.

MeSH terms

  • Animals
  • Behavior, Animal
  • Female
  • Hippocampus / growth & development
  • Hippocampus / metabolism
  • Humans
  • Male
  • Memory Disorders / etiology*
  • Memory Disorders / metabolism
  • Memory Disorders / physiopathology
  • Memory Disorders / psychology
  • Mice
  • Mice, Inbred C57BL
  • Oxidation-Reduction
  • Oxidative Stress
  • Spatial Learning*
  • Tyrosine / adverse effects*
  • Tyrosine / analogs & derivatives*
  • Tyrosine / chemistry*
  • Tyrosine / metabolism

Substances

  • Tyrosine
  • dityrosine