Utjecaj perinatalne primjene prekursora sinteze ili inhibitora razgradnje serotonina na serotoninsku homeostazu u odraslih štakora

doctoral thesis

• Title (english): The effects of perinatal treatment with serotonin synthesis precursor or serotonin degradation inhibitor on the serotonin homeostasis in adult rats
• Author: Sofia Ana Blažević
• Mentor: Dubravka Hranilović (mentor)
• Committee member: Dubravka Švob Štrac (član povjerenstva)
• Committee member: Zoran Tadić (član povjerenstva)
• Committee member: Svjetlana Kalanj-Bognar (član povjerenstva); MBZ: 202561
• Granter: University of Zagreb; Faculty of Science; (Department of Biology); Zagreb
• Defense date and country: 2013, Croatia
• Scientific / art field, discipline and subdiscipline: NATURAL SCIENCES; Biology
• Universal decimal classification (UDC): 577 - Biochemistry. Molecular biology. Biophysics

Abstract

Serotonin (5HT) regulira razvoj vlastitih neurona i ciljnih tkiva tijekom neurogeneze pa odstupanje od optimalnih koncentracija 5HT tijekom razvoja mozga može dovesti do strukturnih i funkcionalnih anomalija. U ovom smo istraživanju kroničnom perinatalnom primjenom neposrednog prekursora sinteze 5HT, 5-hidroksitriptofana (5HTP, 25mg/kg), ili inhibitora razgradnje 5HT, tranilcipromina (TCP, 2mg/kg) povisili razinu 5HT u štakora s ciljem istraživanja posljedica po homeostazu 5HT u odraslom mozgu. Tijekom primjene 5HTP je značajno povisio razinu 5HT samo u perifernom odjeljku (hiperserotoninemija), a TCP i u perifernom i u središnjem odjeljku. Obje primjene uzrokovale su (dugo)trajne posljedice po funkciju središnjeg 5HT-odjeljka, koje su se očitovale kroz promjene u razini i metabolizmu serotonina, ekspresiji 5HT-regulirajućih gena te ponašanja vezanog uz serotonin. Činjenica da su razvojni poremećaji u metabolizmu serotonina (dugo)trajno narušili funkciju središnjeg 5HT-odjeljka upućuje na gene koji reguliraju metabolizam 5HT kao na moguće kandidate u istraživanjima poremećaja ponašanja vezanima uz 5HT sustav. Posljedice dviju primjena bile su analogne, ali su odražavale efekt doze: središnja homeostaza 5HT bila je diskretno narušena u životinja s razvojnim promjenama samo u perifernoj 5HT-homeostazi (5HTP), a opsežno u životinja s razvojnim promjenama i u središnjoj i u perifernoj 5HThomeostazi (TCP). To upućuje na zaključak da je za ozbiljno narušavanje funkcije 5HT, kakvo je opaženo u psihijatrijskim bolestima, nužna razvojna neuravnoteženost u središnjem 5HT-odjeljku i govori u prilog teoriji o hiperserotoninemiji kao o biljegu, a ne uzročniku promjena u središnjoj homeostazi serotonina.

Abstract (english)

Serotonin (5HT) regulates the development of its own neurons and target tissues during neurogenesis, therefore deviations from optimal 5HT concentrations during brain development can lead to structural and functional anomalies. In this thesis, through the chronic perinatal treatment with the immediate serotonin synthesis precursor, 5- hydroxytryptophan (5HTP, 25 mg/kg), or with an inhibitor of 5HT degradation, tranylcypromine (TCP, 2 mg/kg), we have increased 5HT concentrations in rats with the aim of investigating the effects on adult brain 5HT homeostasis. During the treatment 5HTP significantly increased 5HT levels in the peripheral compartment (hyperserotonemia), and TCP in the peripheral and central compartment. Both treatments had long-lasting/permanent consequences on the function of the central 5HT compartment, evident through changes in 5HT concentration and metabolism, expression of 5HT-regulating genes and serotonin related behavior. The fact that developmental disturbances in 5HT metabolism induced permanent disturbances in function of central 5HT compartment points to the genes that regulate 5HT metabolism as potential candidates for research in 5HT-related behavioral disorders. The effects of both treatments where analogous, showing a dose-effect: central 5HT homeostasis was mildly altered in animals with developmental disturbances only in peripheral 5HT homeostasis (5HTP), and drastically altered in animals with developmental disturbances in both central and peripheral 5HT homeostasis (TCP). These findings suggest that severe alterations in 5HT function observed in psychiatric diseases may be caused by developmental disbalance in the central 5HT compartment and speak in favor of the theory of hyperserotonemia as a marker, not a cause, of disturbances in central serotonin homeostasis.

• Keywords: serotonin; 5-hidroksitriptofan; tranilcipromin; hiperserotoninemija; perinatalna primjena
• Keywords (english): serotonin; 5-hydroxytryptophan; tranylcypromine; hyperserotonemia; perinatal treatmen
• Language: croatian
• URN:NBN: urn:nbn:hr:217:510270
• Study programme: Title: Biology; Study programme type: university; Study level: postgraduate; Academic / professional title: doktor/doktorica znanosti, područje prirodnih znanosti, polje biologija (doktor/doktorica znanosti, područje prirodnih znanosti, polje biologija)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Open access
• Created on: 2017-05-18 12:40:39