Metabolic abnormalities of the cortico-striato-thalamo-cortical circuit of rats with tic disorder

Tic disorder (TD) is a developmental neuropsychiatric disorder that primarily occurs during childhood and impacts the quality of life and psychosocial function of patients. The pathogenesis of TD involves the dysregulation of the cortico-striato-thalamo-cortical (CSTC) circuit and metabolic abnormalities may serve an important role. The aim of the present study was to detect and analyze the metabolic abnormalities in the CSTC circuit in TD, providing a reference value for the study of its pathogenesis. A total of 10 male Wistar rats were randomly divided into the control (CK) group (n=5) and the TD group (n=5). Each rat received a daily intraperitoneal injection of 0.9% saline or 3,3'-iminodipropionitrile for 7 consecutive days. Tissues were collected from the striatum and cortex, and ultra-performance liquid chromatography-tandem mass spectrometry was used to measure metabolite concentrations in the brain tissue samples. Significant differences in the metabolites and metabolic pathways of the CK and TD groups were observed. In the striatum, 13 differentially present metabolites were observed between the CK group and TD group, while 21 differentially present metabolites were identified in the cortex. In the CSTC circuit, the common significantly differentially present metabolites were progesterone, corticosterone, deoxycorticosterone, 11-dehydrocorticosterone, chenodeoxycholic acid and hyodeoxycholic acid. The common differentially present metabolic pathways were ‘steroid hormone biosynthesis’ and ‘aldosterone synthesis and secretion’. Notably, the abnormality of the ‘tryptophan metabolism’ pathway was only present in the cortex. These results indicated that there were metabolic abnormalities in the CSTC circuit in TD. The most significantly differentially present metabolite was progesterone. ‘Steroid hormone biosynthesis’ and ‘aldosterone synthesis and secretion’ were the significantly altered metabolic pathways in TD.