Tryptophan-induced effects on the behavior and physiology of aging in tryptophan hydroxylase-2 heterozygous mice C57BL/6N.

Abstract

Background and aim: Tryptophan (Trp), a precursor of serotonin, plays a critical role in cognitive and emotional processes. Its metabolism through serotonin and kynurenine pathways impacts neuropsychiatric functions and lipid metabolism. This study investigates Trp's effects on the behavioral, physiological, and molecular parameters of aging female wild-type (WT) and heterozygous tryptophan hydroxylase-2 (HET) mice.

Materials and methods: A 68-day experiment was conducted on 13-month-old WT and HET mice. Groups received either distilled water or Trp supplementation (400 mg/kg/day). Behavioral tests (Open Field, Elevated Zero Maze, Forced Swim, and Extrapolation Escape Task) assessed locomotion, anxiety, and cognition. Physiological assessments included body composition through NMR relaxometry, lipid histology, serotonin content in the brain (ELISA), and serotonergic gene expression (RT-PCR). Blood biochemistry and organ weights were also analyzed.

Results: Trp supplementation reduced growth rates and adipose tissue while increasing muscle mass in both genotypes, more markedly in HET mice. Behavioral tests revealed a decrease in anxiety and enhanced cognitive performance in HET+Trp mice but an increase in immobility. Trp increased brain serotonin content in HET mice and altered serotonergic gene expression. Histological studies showed hepatoprotective effects in HET+Trp mice, reducing liver lipid infiltration compared to WT+Trp mice.

Conclusion: Trp exhibited genotype-specific effects, with HET mice showing anabolic, hepatoprotective, and neuropsychiatric changes. These findings highlight Trp's potential in neuro-nutrition for conditions like depression and cognitive decline. Further studies are needed to explore Trp's metabolic pathways and their implications for personalized dietary interventions.