Nittoli, Valeria (2016) Behavioural, cellular and molecular insights into hyperexcitability using zebrafish as model system. [Tesi di dottorato]

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Item Type: Tesi di dottorato
Lingua: English
Title: Behavioural, cellular and molecular insights into hyperexcitability using zebrafish as model system
Creators:
CreatorsEmail
Nittoli, Valeriavalerianittoli@libero.it
Date: 30 March 2016
Number of Pages: 94
Institution: Università degli Studi di Napoli Federico II
Department: Medicina Veterinaria e Produzioni Animali
Scuola di dottorato: Scienze veterinarie per la produzione e la sanità
Dottorato: Organismi modello nella ricerca biomedica e veterinaria
Ciclo di dottorato: 28
Coordinatore del Corso di dottorato:
nomeemail
De Girolamo, Paolopaolo.degirolamo@unina.it
Tutor:
nomeemail
Sordino, PaoloUNSPECIFIED
Date: 30 March 2016
Number of Pages: 94
Uncontrolled Keywords: zebrafish; model organisms;
Settori scientifico-disciplinari del MIUR: Area 05 - Scienze biologiche > BIO/11 - Biologia molecolare
Area 05 - Scienze biologiche > BIO/18 - Genetica
Date Deposited: 12 Apr 2016 12:19
Last Modified: 31 Oct 2016 13:38
URI: http://www.fedoa.unina.it/id/eprint/10883

Abstract

Seizures represent the excessive and synchronous neuronal activity in the brain that cause the interruption of normal behaviour and consciousness. While seizures represent the transient manifestation of altered brain functions, epilepsy is a chronic neurologic disorder, characterized by two or more unprovoked or recurrent seizures caused by genetically predetermined process or by an initial insult. Acute and chronic seizures may perturb a wide range of developmental phenomena including cell division, migration, as well as formation and probably stabilization of synapses that are essential for the correct formation and wiring of the circuitry. Both mature and immature rodents have been extensively used to study the cellular and molecular alterations linked to seizures. Recently, the contribution of inflammatory reactions to seizure induction and progression in epilepsy has been formulated, with a particular focus on interleukin 1 beta signalling (IL-1β), suggesting proconvulsant properties of IL-1β in acute seizure activity. Unlike these evidences, other works are consistent with an acute anticonvulsive function of IL-1β in seizure generation. Moreover, several other aspects of the molecular and cellular machineries that promote and define the seizure process, and that derive from them, are not clearly understood. As rodents are among the most frequently used model organisms for seizure and epilepsy studies, other non-mammalian organisms are proposed to tackle these phenomena. Among these, zebrafish is an emerging model system in developmental neurobiology and drug discovery. Recent studies have described that both larval and adult zebrafish develop seizures when exposed to chemoconvulsant agents, and they present similar profiles of responsiveness to anticonvulsant compounds, enlightening the potential of zebrafish models for the in vivo study of brain functions and dysfunction. The aim of my PhD project is to characterize the induction of seizures in the embryonic brain of zebrafish, using a known proconvulsant agent, pentylenetetrazole (PTZ). First, I have described the transcriptional, morphological and behavioural responses associated with neuronal hyperactivity during the period of structural and physiological maturation of the brain. Then, I have investigated the eventual contribution of inflammatory reactions in seizure induction, with a particular regard to gaining novel insights on the role of IL-1β signalling in seizures in fish.

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