TY - JOUR

T1 - Role of Glial Trace Amine Associated Receptor 1 (TAAR1) and Microbiota in Schizophrenia

AU - Tsytsarev, V.

AU - Ваганова, Анастасия Николаевна

AU - Вольнова, Анна Борисовна

AU - Фесенко, Зоя Сергеевна

AU - Getachew, Bruk

AU - Гайнетдинов, Рауль Радикович

AU - Tizabi, Yousef

PY - 2025/10/1

Y1 - 2025/10/1

N2 - Trace amine-associated receptors (TAARs) are a class of G protein-coupled receptors that respond to metabolic derivatives of the amino acids such as phenylalanine, tyrosine, and tryptophan. Trace amines derive their name from the fact that their concentration in the periphery as well as in the central nervous system (CNS) is in trace amounts compared to the parent compound or other monoamine neurotransmitters such as dopamine, norepinephrine, or serotonin. Genetic, pharmacological and neurobiological studies have linked TAAR1, the most studied receptor of the TAARs to the pathophysiology of schizophrenia (SCZ), the current treatments of which are limited. Recent developments in the field implicate glial-microbiota interactions in SCZ pathophysiology. TAAR1 interactions with the glial cells and the gut microbiota (GM) makes it a suitable candidate as a novel target in SCZ. In this review, following brief descriptions of the known neurobiological substrates of SCZ, we delve into the specific roles of glial cells, including analysis of the public transcriptomic data, their interaction with GM and the potential integrator role of TAAR1 in glial-GM signaling relevant to SCZ. Finally, we suggest how TAAR1 manipulation may be exploited in this devastating neuropsychiatric disorder.

AB - Trace amine-associated receptors (TAARs) are a class of G protein-coupled receptors that respond to metabolic derivatives of the amino acids such as phenylalanine, tyrosine, and tryptophan. Trace amines derive their name from the fact that their concentration in the periphery as well as in the central nervous system (CNS) is in trace amounts compared to the parent compound or other monoamine neurotransmitters such as dopamine, norepinephrine, or serotonin. Genetic, pharmacological and neurobiological studies have linked TAAR1, the most studied receptor of the TAARs to the pathophysiology of schizophrenia (SCZ), the current treatments of which are limited. Recent developments in the field implicate glial-microbiota interactions in SCZ pathophysiology. TAAR1 interactions with the glial cells and the gut microbiota (GM) makes it a suitable candidate as a novel target in SCZ. In this review, following brief descriptions of the known neurobiological substrates of SCZ, we delve into the specific roles of glial cells, including analysis of the public transcriptomic data, their interaction with GM and the potential integrator role of TAAR1 in glial-GM signaling relevant to SCZ. Finally, we suggest how TAAR1 manipulation may be exploited in this devastating neuropsychiatric disorder.

KW - Astrocytes

KW - Gut microbiota

KW - Microglia

KW - Neuroinflammation

KW - Schizophrenia

KW - TAAR1

KW - Trace amine associated receptors

KW - Humans

KW - Schizophrenia/metabolism

KW - Neuroglia/metabolism

KW - Trace Amine-Associated Receptors

KW - Animals

KW - Receptors, G-Protein-Coupled/metabolism

KW - Gastrointestinal Microbiome/physiology

UR - https://www.mendeley.com/catalogue/34f78846-ce68-37d2-86a9-cb4f013e9ace/

U2 - 10.1007/s11064-025-04525-5

DO - 10.1007/s11064-025-04525-5

M3 - Review article

C2 - 40839091

VL - 50

JO - Neurochemical Research

JF - Neurochemical Research

SN - 0364-3190

IS - 5

M1 - 273

ER -