C1473G Polymorphism in Tph2 Gene Affects Activation of Serotonin Metabolism in Mouse Brain 24 h after LPS Administration.

Abstract

We studied the effect of the C1473G polymorphism in the Tph2 gene that reduces the activity of the tryptophan hydroxylase 2 in the brain on the severity of changes in motor activity (23 h after intraperitoneal administration of 0.8 mg/kg LPS or saline) and on the level of serotonin (5-HT) and its metabolite 5-hydroxyindoleacetic acid (5-HIAA) in the endings of 5-HT neurons in the cortex, hippocampus, and striatum (24 h after administration) of mature male mice of congenic lines B6-1473CC (high activity) and B6-1473GG (low activity). The state of the immune system in these structures was assessed by the expression of genes for proinflammatory cytokines IL-1β and TNF. LPS caused a decrease in motor and exploratory activities and increased the expression of the Il1b and Tnf genes in the studied brain structures in mice of both genotypes. LPS did not affect the level of 5-HT in any of the studied brain structures, but dramatically increased the level of 5-HIAA in these structures. The influence of the C1473G polymorphism on the intensity of the LPS-dependent increase in the level of 5-HIAA in the cortex and striatum was shown: in B6-1473CC mice this increase was more pronounced than in B6-1473GG mice. Demonstration of the influence of this polymorphism on the response of the 5-HT system after stimulation of the innate immunity is important for understanding of the role of tryptophan hydroxylase 2 in the mechanism of adaptation of the nervous system during infections and for predicting and reducing the risks of mental disorders.