Adult rat jejunum and liver histological measurements and gene expression after perinatal exposure 5-hydroxytryptophan and tranylcypromine

Maintaining serotonin (5HT) homeostasis is vital for physiological processes in the central nervous system and peripheral tissues. Hyperserotonemia, a measurable sign of 5HT homeostasis disruption that can be caused by 5HT-directed treatments for psychiatric and gastrointestinal disorders, has unresolved implications for long-term 5HT equilibrium in the periphery. This study investigates perinatal 5HT imbalance effects on jejunum and liver in adult rats. Hyperserotonemia was induced by 5-hydroxytryptophan (5HTP) or tranylcypromine (TCP) treatment. At postnatal day 70, jejunum and liver samples were analyzed. Compared to controls, 5HTP and TCP-treated rats showed reduced 5HT-producing cells and decreased jejunum 5HT-synthesizing enzyme expression. Additionally, there was increased 5HT transporter expression with hepatocyte karyomegaly, more pronounced in TCP-treated animals. This study reveals lasting cellular and molecular changes due to perinatal 5HT imbalance, potentially impacting 5HT availability in the periphery. The rat model links developmental serotonin abnormalities to adult 5HT-related changes, offering insights into susceptibility to behavioral and metabolic disorders. It serves as a model for exploring adverse effects of prenatal exposure to 5HT enhancers in humans.

The study involved a two-step chronic treatment of animals with either of the two 5HT enhancers—5-hydroxytryptophan (5HTP) and tranylcypromine (TCP)—or saline. In the first step, pregnant females (3 with each 5HT enhancer and 2 with saline) were treated from gestational day 12 until parturition. In the second step, pups (13 with TCP, 13 with 5HTP, and 11 with saline) were treated from postnatal day (PND) 1 until PND21. At PND70, blood, jejunum, and liver samples were collected from all experimental and control rats. Serum 5HT concentrations were measured with ELISA, and jejunum and liver tissues were examined histomorphologically. The relative expression of genes related to the serotonin pathway proteins, including tryptophan hydroxylase 1 (Tph1) and vesicular monoamine transporter 1 (Vmat1) responsible for serotonin synthesis and storage in the jejunum, and serotonin transporter (5HTt) and monoamine oxidase A (MaoA) responsible for 5HT elimination in the liver, was determined via quantitative PCR.