Advanced search
Start date

Impact of subconvulsive doses of pentylenetetrazole in the zebrafish ("Danio rerio") immature brain

Full text
Katia Silva de Brito
Total Authors: 1
Document type: Master's Dissertation
Defense date:
Advisor: Claudia Vianna Maurer Morelli

Epilepsies are common neurological disorders in which the brain activity became abnormal, leading to unprovoked seizures. The majority of our understanding of neurobiological aspects of human epilepsies come from the animal models, especially from the epileptogenesis models. Zebrafish (Danio rerio) has been choosen for many studies because of its advantages for scientific experimentation, mainly in genetic investigations. The most widely used animal models for studying epilepsy are rodents. Recently, zebrafish has been shown to be able to present behavior pattern, molecular and electrographic modifications that mimic acute seizures, making zebrafish a promising model for investigations of epilepsies. Despite its advantages, there is still no description showing that this animal can become chronically epileptic. In this way, it is reasonable to use the kindling method for create a chronic epilepsy zebrafish model. Kindling is a process in which the brain of an animal model is often stimulated, electrically or chemically, thus creating conditions that increase the brain's susceptibility to become chronically epileptic. The kindling model is already well explored in rodents, and offers a great opportunity to investigate the mechanisms underlying the epileptogenesis. This exploratory study aimed to apply a chemical kindling protocol in zebrafish through the daily administration of subconvulsivant doses of pentylenetetrazole (PTZ) at a concentration of 7.5 mM for 2 minutes during 60 days followed by behavioral and molecular analyses, as well as by investigating the levels of transcripts of the genes: c-fos, fosb, cox2, klrn and il1b by real-time PCR at four different time-points. The behavioral analysis showed that the animals did not present significant alterations of the standard behavior already described for seizure-induced zebrafish model. In molecular analysis there was a significant increase in the c-fos expression at the 5th and 60th days of the treatment indicating that there is an increase in neuronal recruitment, but that does not reproduce epilepsy. The klrn gene was shown to be ldown regulated on the 15th day. Other genes investigated did not present significant alterations. Our results showed that zebrafish did not present spontaneous seizures, which may be indicative of resistance to treatment. Confirmation of these findings and investigation of the mechanisms underlying the zebrafish?s resistance to the kindling may contribute to the identification of new targets for epilepsies treatment in humans (AU)

FAPESP's process: 14/15640-8 - Functional studies of genes of inflammation and microRNAs related to seizures using the zebrafish model
Grantee:Cláudia Vianna Maurer Morelli
Support type: Regular Research Grants