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

Area of Science:

• Neuroscience
• Biochemistry
• Toxicology

Background:

• Oxidized tyrosine products (OTPs) are increasingly prevalent in modern diets due to food processing.
• Dityrosine (DT) is a major component of OTPs, and its biological effects are not fully understood.

Purpose of the Study:

• To investigate the neurotoxic effects of OTPs and DT in the developing brain.
• To assess the impact of OTPs and DT on learning, memory, and behavior in mice.

Main Methods:

• Growing mice (male and female) were administered tyrosine (control), DT, or OTPs via intragastric gavage for 35 days.
• Evaluated brain redox state, inflammatory markers, oxidative damage, neurotransmitter levels, and gene expression in the hippocampus.
• Assessed behavioral outcomes including learning, memory, response latency, and anxiety-like behaviors.

Main Results:

• DT and OTPs induced redox imbalance, inflammation, and oxidative damage in the hippocampus.
• Treatment led to neurotransmitter disorders, activation of mitochondrial apoptosis, and downregulation of learning/memory genes.
• Mice exposed to DT and OTPs exhibited impaired learning and memory, delayed responses, and anxiety-like behaviors.
• Male mice showed slightly greater oxidative damage compared to females.

Conclusions:

• Dietary intake of OTPs and DT adversely affects brain development and function in growing mice.
• These findings highlight the potential risks of oxidized proteins in food and suggest a need for dietary modification.
• Reducing oxidized protein consumption may be crucial for preventing neurodevelopmental and behavioral issues.