Neonatal viral brain infection and the development of prepulse inhibition : a neurodevelopmental model of schizophrenia

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http://urn.fi/URN:NBN:fi-fe20031204
Title: Neonatal viral brain infection and the development of prepulse inhibition : a neurodevelopmental model of schizophrenia
Author: Aitta-aho, Teemu
Other contributor: Helsingin yliopisto, Matemaattis-luonnontieteellinen tiedekunta, Farmasian laitos
University of Helsinki, Faculty of Science, Department of Pharmacy
Helsingfors universitet, Matematisk-naturvetenskapliga fakulteten, Farmaceutiska institutet
Publisher: Helsingfors universitet
Date: 2003
Language: eng
URI: http://urn.fi/URN:NBN:fi-fe20031204
http://hdl.handle.net/10138/19176
Thesis level: master's thesis
Discipline: Farmakologi och toxikologi
Pharmacology and toxicology
Farmakologia ja toksikologia
Abstract: Epidemiological data suggest an important role of perinatal viral infections in the etiology of schizophrenia. In this thesis the connection between neonatal viral brain infection and its consequences to the development of central nervous system was studied. In schizophrenia the symptoms are divided into three categories as positive, negative and cognitive ones. Positive symptoms refer to hallucinations and delusions, negative symptoms are defined as social withdrawal, apathy and poor motivation and cognitive symptoms include deficits in abstraction and paying attention into subjects. Symptoms suggest that in schizophrenia the received information can not be filtered properly in central nervous system, but comes into patients senses in excess i.e. there are defects in sensorimotor gating. Sensorimotor gating was studied by prepulse inhibition of acoustic startle -phenomenon. Prepulse inhibition refers to the inhibition of the startle reflex by weak prepulse presented before the startling stimulus. In schizophrenic patients prepulse inhibition is decreased and in addition to that psychotomimetic drugs disrupt prepulse inhibition in humans as well as in experimental animals. Sensorimotor gating ability is developed under neuronal development and it can be affected by several neurodevelopmental disturbances. In the present study rats were infected with herpes simplex type 1 virus at neonatal age and later challenged to dopaminergic and glutamatergic systems. Results show controversial data of effects on prepulse inhibition, still some attenuation can be seen. Challenge studies did not show clear and persistent effect either in dopaminergic or glutamatergic tests. Corticosterone, naturally occurring hormone in rats, was administered to rat mothers under gestation until weaning in terms to clarify its effects to neuronal development. Administration was carried out by implanted pellet as well as by drinking water. The latter was found to work out better as it releases corticosterone in pulsatile manner. Corticosterone was administered also in acute test to drug naïve animals. This test showed significant decrease on prepulse inhibition. The same could not be repeated in corticosterone challenge test after perinatal treatments. Nitric oxide synthase inhibitor L-NMMA was administered to neonates under days 5-9 after partus. This was supposed to prevent neonates from neurodevelopmental disturbances affected by virus and corticosterone. Despite various dose levels used, any clear effect could not be seen. In summary, the studies show some effect of treatments on neuronal development and sensorimotor gating measured by prepulse inhibition. In the test groups inspected many treatments showed effect at first, but those effects disappeared at later tests as rats grew up. This might be an outcome of the potential compensatory mechanisms of the central nervous system to counteract harmful neurodevelopmental events.
Subject: schizophrenia
prepulse inhibition
herpes simplex virus
perinatal viral infection
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