engleski

Molecular background and physiological consequences of altered peripheral 5-HT homeostasis in adult rats perinatally treated with tranylcypromine

Developmental exposure to 5-HT-enhancing agents has been reported to induce long-lasting changes in the brain, but there is hardly any data on the long-term effects of perinatal 5-HT enhancement on 5-HT balance and function in the peripheral compartment. Perinatal treatment of rats with monoamine oxidase (MAO) inhibitor tranylcypromine (TCP), leads to persistent imbalance in central (increased 5-HT degradation and decreased 5-HT concentrations in the brain) and peripheral (increased platelet and decreased plasma 5-HT concentrations) 5-HT homeostasis. In this study, we explored the molecular background of peripheral serotonin imbalance, and its possible consequences on bone remodelling and haematopoiesis. Jejunum, liver and blood samples were collected from TCP- and saline- treated rats on post-natal day 70. Relative mRNA levels for tryptophan hydroxylase 1 (TPH1) and MAO A were analysed using quantitative RT- PCR, femoral trabecular bone parameters were measured using micro-computed tomography, while peripheral blood cell number was determined by cell counter. TCP-treated rats displayed significant decrease in expression of Tph1, and significant increase in percentage of bone volume, trabecular number, connectivity density, and leukocyte number. Significant negative correlation was observed between relative concentrations of TPH1 mRNA and trabecular bone parameters. Significant long- lasting decrease in the intestinal Tph1 expression, along with accumulation of 5-HT into platelets, may represent the main mechanism of peripheral compensation for 5-HT excess during treatment, presumably leading to increase in trabecular bone structure (supporting the negative influence of peripheral 5-HT on bone accrual) and leukocyte number (indicating negative in vivo effect of 5-HT in regulation of leukocyte development and/or sustainment).

serotonin; tranylcypromine; qRT-PCR; bone remodelling

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