TY - JOUR

T1 - Protein Metabolism Changes and Alterations in Behavior of Trace Amine-Associated Receptor 1 Knockout Mice Fed a High-Fructose Diet

AU - Apryatin, Sergey A.

AU - Zhukov, Ilya S.

AU - Zolotoverkhaya, Ekaterina A.

AU - Kuvarzin, Saveliy R.

AU - Khunagov, Temirkan A.

AU - Ushmugina, Sanelya V.

AU - Klimenko, Victor M.

PY - 2023/2/28

Y1 - 2023/2/28

N2 - Trace amines and their receptors are a family of G protein-coupled receptors widely distributed in the central nervous system and periphery. The trace amine-associated receptor 1 (TAAR1) plays a significant role as a therapeutic target for schizophrenia, depression, diabetes, and obesity. In this study, TAAR1 knockout mice and WT groups were tested in conditions of a high-fructose diet. The consumption of a high-fructose diet may be due to the influence on the metabolism processes by dopamine in the brain, neuromotor function, and level of anxiety of TAAR1 knockout mice. During a comparative analysis of behavioral, biochemical, and morphological parameters, significant differences were found between liver and biochemical parameters, the regulation of protein metabolism (AST/ALT ratio, creatine kinase activity, urea), and alterations in behavior. An elevated plus maze analysis showed the influence of fructose and genetic factors on the level of anxiety. A new marker of the grooming microstructure (depression ratio) was tested, which showed high efficiency as a marker of depression-like behavioral changes and a possible association with dopamine-dependent regulation of protein metabolism. These results confirm a possible association of the TAAR1 gene knockout with an increase in catabolic reaction levels by AST/ALT-dependent and possible dopamine-mediated protein metabolism regulation and depression-like behavior.

AB - Trace amines and their receptors are a family of G protein-coupled receptors widely distributed in the central nervous system and periphery. The trace amine-associated receptor 1 (TAAR1) plays a significant role as a therapeutic target for schizophrenia, depression, diabetes, and obesity. In this study, TAAR1 knockout mice and WT groups were tested in conditions of a high-fructose diet. The consumption of a high-fructose diet may be due to the influence on the metabolism processes by dopamine in the brain, neuromotor function, and level of anxiety of TAAR1 knockout mice. During a comparative analysis of behavioral, biochemical, and morphological parameters, significant differences were found between liver and biochemical parameters, the regulation of protein metabolism (AST/ALT ratio, creatine kinase activity, urea), and alterations in behavior. An elevated plus maze analysis showed the influence of fructose and genetic factors on the level of anxiety. A new marker of the grooming microstructure (depression ratio) was tested, which showed high efficiency as a marker of depression-like behavioral changes and a possible association with dopamine-dependent regulation of protein metabolism. These results confirm a possible association of the TAAR1 gene knockout with an increase in catabolic reaction levels by AST/ALT-dependent and possible dopamine-mediated protein metabolism regulation and depression-like behavior.

KW - AST/ALT ratio

KW - G protein-coupled receptors

KW - TAAR1

KW - catabolism

KW - depression

KW - depression ratio

KW - dopamine

KW - energy metabolism

KW - high-fructose diet

KW - liver

KW - trace amine-associated receptor 1

UR - https://www.mendeley.com/catalogue/5d2478dc-1a30-332a-b229-f348c4ec15e4/

U2 - 10.3390/neurolint15010022

DO - 10.3390/neurolint15010022

M3 - Article

C2 - 36976665

VL - 15

SP - 339

EP - 351

JO - Neurology International

JF - Neurology International

SN - 2035-8385

IS - 1

ER -