Naslov
Animal model of hyperserotonemia: the relationship between disturbed peripheral 5HT homeostasis and central 5HT function

Autori
Blažević, Sofia

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, neobjavljeni rad, ostalo

Skup
International Symposium: Genes and Autism

Mjesto i datum
Split, Hrvatska, 05.10.2010. - 09.10.2010

Vrsta sudjelovanja
Pozvano predavanje

Vrsta recenzije
Nije recenziran

Ključne riječi
autism; hyperserotonemia; rat; pharmacological treatment; serotonin

Sažetak
Serotonin (5-hydroxytryptamine, 5HT) is present both, in brain and peripheral tissues where it mediates various physiological functions. It also regulates the perinatal development of serotonergic neurons and target tissues. Alterations in 5HT neurotransmission are indicated as biological substrates in several neuropsychiatric disorders, including autism. The most consistent 5HT-related finding in autistic disorder is hyperserotonemia (elevated blood 5HT concentration), but the mechanism of its development and its relation to central 5HT dysfunction are still unclear. One of the aims of the project “Neurobiological basis of autism: The role of serotonin system” is to study the effects of increased serotonin levels during perinatal development on serotonin homeostasis in adult rats. In our attempt to model hyperserotonemia, hyperserotonemia was pharmacologically induced in rats during the period of most intensive development of 5HT neurons (from gestational day 12 through postnatal day 21) using either the immediate 5HT precursor, 5-hydroxytryptophan (5HTP), or the non-selective irreversible MAO inhibitor tranylcypromine (TCP). The animals from both treatment groups had lower survival rate and slower weight gain. Blood serotonin levels, measured with ELISA, were increased in both groups at the end of treatment establishing that the treatments did cause hyperserotonemia. The perinataly induced hyperserotonemia lasted into adulthood only in the TCP treated group. Brain serotonin levels, measured with HPLC-EC, were increased at the end of treatment in the frontal cortices of pups treated with TCP but not in those treated with 5HTP. In adulthood, mean 5HT levels of the TCP treated animals were markedly decreased compared to controls in both, raphe nuclei and frontal cortex. TCP treatment also chronically decreased 5HT synthesis and increased 5HT degradation in both the raphe nuclei and frontal cortex. The 5HTP treatment seemed to significantly lower 5HT levels in frontal cortex, but not in the raphe region, and it did not affect either the synthesis or the degradation rate of 5HT. From these results we assume that the effects of the TCP treatment were caused by simultaneous disregulation of the serotonin system in both compartments. Similarly, we assume that the effects of the 5HTP treatment are the result of hyperserotonemia induced inhibition of branching of serotonergic neurons. This leads us to conclude that the simultaneous central and peripheral changes in expression/function of a 5-HT regulating element might be the underlying cause in the 5HT-dysregulation seen in autism.

Izvorni jezik
Engleski

Znanstvena područja
Biologija

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