Vet World   Vol.18   February-2025  Article - 6 

Research Article

Veterinary World, 18(2): 296-310

https://doi.org/10.14202/vetworld.2025.296-310

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

Anastasiya Kibitkina1, Ekaterina Vasilevskaya1, Galina Tolmacheva1, Elena Kotenkova2, Ekaterina Polishchuk1, Viktoriya Pchelkina1, Sergey Karabanov1, and Liliya Fedulova1
1. Department of Experimental Clinic and Research Laboratory for Bioactive Substances of Animal Origin, V.M. Gorbatov Federal Research Center for Food Systems, Moscow, Russia.
2. Center for Genomic Technology and Bioinformatics, Moscow Institute of Physics and Technology (National Research University), Dolgoprudny, Russia.

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.

Keywords: aging, behavioral tests, lipid metabolism, neuro-nutrition, neuropsychiatry, serotonin, tryptophan hydroxylase-2 heterozygosity, tryptophan.


How to cite this article: Kibitkina A, Vasilevskaya E, Tolmacheva G, Kotenkova E, Polishchuk E, Pchelkina V, Karabanov S, and Fedulova L (2025) Tryptophan-induced effects on the behavior and physiology of aging in tryptophan hydroxylase-2 heterozygous mice C57BL/6N, Veterinary World, 18(2): 296-310.

Received: 2024-08-16    Accepted: 2025-01-10    Published online: 2025-02-13

Corresponding author: Sergey Karabanov    E-mail: karabans89@gmail.com

DOI: 10.14202/vetworld.2025.296-310

Copyright: Kibitkina, et al. This article is an open access article distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/ by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http:// creativecommons.org/ publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.