Kainate administered to adult zebrafish causes seizures similar to those in rodent models

Abstract

Glutamate is the major excitatory neurotransmitter of the central nervous system in vertebrates. Excitotoxicity, caused by over-stimulation of the glutamate receptors, is a major cause of neuron death in several brain diseases, including epilepsy. We describe here how behavioural seizures can be triggered in adult zebrafish by the administration of kainate and are very similar to those observed in rodent models. Kainate induced a dose-dependent sequence of behavioural changes culminating in clonus-like convulsions. Behavioural seizures were suppressed by DNQX (6,7-dinitroquinoxaline-2,3-dione) dose-dependently, whilst MK-801 (a non-competitive NMDA receptor antagonist) had a lesser effect. Kainate triggers seizures in adult zebrafish, and thus this species can be considered as a new model for studying seizures and subsequent excitotoxic brain injury.

Zebrafish as an animal model in epilepsy studies with multichannel EEG recordings

“…Because of these advantages, zebrafish have been used in human disease studies, including haematological disorders, solid tumours, heart disorders, muscle disorders, kidney disorders, central nervous system disorders, and ocular disorders 10,16 . In epilepsy studies, seizure events resemble those in human, mouse, rat, and zebrafish 17,18 .…”

“…For example, use of embryonic zebrafish in certain therapies that are applicable in bigger animals is limited; deep brain stimulation and delicate EEG montage calibration are impossible. Because electrophysiological tools are limited in zebrafish studies, most epilepsy studies using adult zebrafish focus on behavioural studies 18,26,27 . Studies using adult zebrafish can accelerate new AED research and unveil the mechanisms underlying epilepsy due to their fully developed behavioural repertoires and central nervous system 28 .…”

Enhanced characterization of the zebrafish brain as revealed by super-resolution track-density imaging

“…Large clutch sizes, transparent larval stages, and the ability to perform forward or reverse genetic analyses have particularly facilitated the use of embryonic and larval zebrafish (Lieschke and Currie 2007). Mature zebrafish, which possess well-developed endocrine, sensory, and motor systems (Bally-Cuif and Vernier 2010), a range of complex behaviours such as social interactions (Saverino and Gerlai 2008), learning and memory (Gomez-Laplaza and Gerlai 2010; Norton and Bally-Cuif 2010;Al-Imari and Gerlai 2008) and a physiology similar to mammals (Bally-Cuif and Vernier 2010), have been recognized as beneficial to investigations of neurological diseases (Alfaro et al 2011;Siebel et al 2011;Wong et al 2010;Keller and Murtha 2004;Mathur and Guo 2010;Ramirez et al 2012;Haud et al 2011;Williams et al 2011). As adult zebrafish continue to be used as an experimental model, new techniques are being developed to better characterize their behaviour , neuronal activity (Pineda et al 2011), neurochemistry (Kabli et al 2009) and neuromorphology (Rao et al 2009;Ullmann et al 2010b;Ullmann et al 2010a; Kabli et al 2006).…”

Building a zebrafish toolkit for investigating the pathobiology of epilepsy and identifying new treatments for epileptic seizures

“…Within just a few minutes of treating zebrafish larvae or adults with PTZ, epileptiform discharges and immediate-early gene expression are detectable in the brain, and accompanied by vigorous locomotor convulsive behaviours (Baraban et al, 2005;Mussulini et al, 2013;Afrikanova et al, 2013). PTZ has become the most widely used and extensively validated pharmacological inducer of acute seizures in zebrafish, but it is only one of a wide range of chemicals that have been shown to induce seizures and convulsions in zebrafish (Winter et al, 2008), and further studies have extended this range to include other well-characterized experimental convulsants which are known to be effective in mammals, such as Kainic Acid (Alfaro et al, 2011), its marine neurotoxin analogue Domoic Acid (Tiedeken and Ramsdell, 2007), the plant natural product ginkgotoxin (Lee et al, 2012) and Allyl-Glycine (Leclercq et al, 2015). Thus, many compounds that provoke seizures in mammals, do so with comparable efficacy in zebrafish.…”