Molecular background and physiological consequences of altered peripheral serotonin homeostasis in adult rats perinatally treated with tranylcypromine.
Serotonin (5-hydroxytryptamine, 5-HT) is a biologically active molecule present in mammals in the brain and peripheral tissues where it exerts many physiological functions. Developmental exposure to 5-HT-enhancing agents has been reported to induce long-lasting changes in the brain, but the long-term effects of perinatal 5-HT enhancement on 5-HT balance and function in the peripheral compartment have not been explored. 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 5-HT imbalance, and its possible consequences on bone remodeling and hematopoiesis. 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 analyzed using quantitative RT-PCR, femoral trabecular bone parameters were measured using microcomputed 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. In addition, significant negative correlation was observed between relative concentrations of TPH1 mRNA and trabecular bone parameters. Our results: a) show that perinatal exposure to tranylcypromine leads to long-lasting compensatory decrease in Tph1 expression in the peripheral compartment, accompanied with alterations in bone remodeling and hematopoiesis, b) suggest that peripheral and central 5HT compartment use different strategies to compensate for 5-HT imbalances of the same cause, and c) indicate dominant role of peripheral over central 5-HT in the regulation of bone maintenance, as well as possible negative in vivo influence of peripheral 5-HT on leukocyte development and/or sustainment.
Division of Animal Physiology, Department of Biology, University of Zagreb Faculty of Science; Zagreb, Croatia.
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Blazevic
Laboratory for Mineralized Tissues, Centre for Translational and Clinical Research, University of Zagreb School of Medicine; Zagreb, Croatia.
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Erjavec
Division of Animal Physiology, Department of Biology, University of Zagreb Faculty of Science; Zagreb, Croatia.
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Brizic
Laboratory for Mineralized Tissues, Centre for Translational and Clinical Research, University of Zagreb School of Medicine; Zagreb, Croatia.
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Vukicevic
Division of Animal Physiology, Department of Biology, University of Zagreb Faculty of Science; Zagreb, Croatia. dubravka@biol.pmf.hr.
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Hranilovic
D000818:Animals; D000831:Animals, Newborn; D001772:Blood Cell Count; D001792:Blood Platelets / Q000187:drug effects / Q000201:enzymology; D016723:Bone Remodeling / Q000187:drug effects; D001842:Bone and Bones / Q000187:drug effects / Q000378:metabolism; D005260:Female; D006706:Homeostasis / Q000187:drug effects*; D008297:Male; D008995:Monoamine Oxidase / Q000096:biosynthesis; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology*; D017933:Peripheral Nervous System / Q000187:drug effects* / Q000378:metabolism*; D011247:Pregnancy; D051381:Rats; D017208:Rats, Wistar; D012701:Serotonin / Q000378:metabolism*; D012727:Sex Characteristics; D014191:Tranylcypromine / Q000494:pharmacology*; D014365:Tryptophan Hydroxylase / Q000096:biosynthesis / Q000235:genetics
D008996:Monoamine Oxidase Inhibitors; D012701:Serotonin; D014191:Tranylcypromine; D014365:Tryptophan Hydroxylase; C504570:tph1 protein, rat; D008995:Monoamine Oxidase