Naslov
Changes in expression and activity of 5HT-regulating proteins in brains of hyperserotonemic rats

Autori
Blazević, Sofia ; Orešković, Darko ; Hranilović, Dubravka

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, znanstveni

Izvornik
FEBS3+ Meeting “From molecules to life and back” / Dumić, Jerka ; Kovarik, Zrinka ; Varljen, Jadranka - Rijeka : Hrvatsko Društvo za Biotehnologiju, 2012

ISBN
978-953-95551-4-4

Skup
FEBS3+ Meeting “From molecules to life and back”

Mjesto i datum
Opatija, Hrvatska, 13.06.2012. - 16.06.2012

Vrsta sudjelovanja
Poster

Vrsta recenzije
Međunarodna recenzija

Ključne riječi
gene expression; serotonin; 5HT-regulating proteins; hyperserotonemia

Sažetak
Serotonin (5-hydroxytryptamine, 5HT) has two important roles in the mammalian brain: it regulates serotonergic outgrowth and maturation of the target regions in the developing brain, and modulates function and plasticity of the adult brain. Several lines of evidence suggest that alterations in the serotonergic neurotransmitter system might represent one of the biological substrates of Autism. The most consistent 5HT-related finding in Autism is hyperserotonemia (elevated blood 5HT levels) paralleled with altered brain serotonin synthesis, but the relationship between the 5HT disturbances in the two compartments is not understood. The aim of this study was to pharmacologically induce hyperserotonemia in rats during the period of most intensive development of 5HT neurons - from gestational day 13 to post-natal day (PND) 21 - using either the immediate 5HT precursor, 5-hydroxytryptophan (5HTP, 25 mg/kg), or the non-selective irreversible MAO inhibitor tranylcypromine (TCP, 2 mg/kg). The treatment was successful in inducing permanent hyperserotonemia that lasted into adulthood. In the raphe nuclei of adult rats, 5HT and 5-hydroxyindol acetic acid (5HIAA) concentrations were measured by high-performance liquid chromatography with electrochemical detection and expressed per g of wet tissue ; and gene expression analyses were made with qRT-PCR using Taq-man chemistry. Although the 5HTP treated group had a significant increase in monoamine oxidase (MAO) A gene expression, no significant changes were observed in midbrain serotonin levels or metabolism. In TCP treated rats, gene expression of MAO A and B was very significantly increased in comparison to the control group, and this was biochemically reflected in a strong decrease in 5HT concentrations and a great increase in 5HIAA/5HT ratio indicating the level of 5HT metabolism. We suppose that the perinatal inhibition of MAO A and B induced compensatory changes in the expression of their genes leading to a permanently disturbed 5HT homeostasis in rats. These results speak in favor of the theory that possible alterations in the expression of one or more of the 5HT elements could lead to the dysregulation of 5HT transmission in the brain (affecting so its early development and resulting in autistic behavioral symptoms), while it is at the same time reflected in the periphery as hyperserotonemia.

Izvorni jezik
Engleski

Znanstvena područja
Biologija

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