Assessing Epilepsy-Related Behavioral Phenotypes in Adult Zebrafish

Desmond, Daniel; Kyzar, Evan J.; Gaikwad, Siddharth; Green, Jeremy; Riehl, Russell; Roth, Andrew; Stewart, Adam; Kalueff, Allan V.

doi:10.1007/978-1-61779-597-8_24

Cited by 10 publications

(9 citation statements)

References 27 publications

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“…Pentylenetetrazole is a chemoconvulsant act via GABA A receptor and act on an allosteric site ( Desmond et al, 2012 ). A dose of 220 mg/kg of PTZ produce clonic tonic seizure in adult zebrafish ( Banote et al, 2013 ).…”

Section: Discussionmentioning

confidence: 99%

“…Pentylenetetrazole (PTZ) is used in zebrafish to induce epileptic seizure-like condition and to study the mechanisms of seizures ( Desmond et al, 2012 ). γ-aminobutyric acid (GABA) is the major inhibitory neurotransmitter in the brain, PTZ exerts its convulsive effect by inhibiting the activity of GABA at GABA A receptors ( Shaikh et al, 2013 ).…”

Section: Introductionmentioning

confidence: 99%

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Zebrafish as a Model for Epilepsy-Induced Cognitive Dysfunction: A Pharmacological, Biochemical and Behavioral Approach

et al. 2017

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Epilepsy is a neuronal disorder allied with distinct neurological and behavioral alterations characterized by recurrent spontaneous epileptic seizures. Impairment of the cognitive performances such as learning and memory is frequently observed in epileptic patients. Anti-epileptic drugs (AEDs) are efficient to the majority of patients. However, 30% of this population seems to be refractory to the drug treatment. These patients are not seizure-free and frequently they show impaired cognitive functions. Unfortunately, as a side effect, some AEDs could contribute to such impairment. The major problem associated with conducting studies on epilepsy-related cognitive function is the lack of easy, rapid, specific and sensitive in vivo testing models. However, by using a number of different techniques and parameters in the zebrafish, we can incorporate the unique feature of specific disorder to study the molecular and behavior basis of this disease. In the view of current literature, the goal of the study was to develop a zebrafish model of epilepsy induced cognitive dysfunction. In this study, the effect of AEDs on locomotor activity and seizure-like behavior was tested against the pentylenetetrazole (PTZ) induced seizures in zebrafish and epilepsy associated cognitive dysfunction was determined using T-maze test followed by neurotransmitter estimation and gene expression analysis. It was observed that all the AEDs significantly reversed PTZ induced seizure in zebrafish, but had a negative impact on cognitive functions of zebrafish. AEDs were found to modulate neurotransmitter levels, especially GABA, glutamate, and acetylcholine and gene expression in the drug treated zebrafish brains. Therefore, combination of behavioral, neurochemical and genenetic information, makes this model a useful tool for future research and discovery of newer and safer AEDs.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Zebrafish as a Model for Epilepsy-Induced Cognitive Dysfunction: A Pharmacological, Biochemical and Behavioral Approach

et al. 2017

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“…3D). To further test whether tsc2 vu242/vu242 are more susceptible to seizures, we exposed tsc2 vu242 fish to γ-aminobutyric-acid receptor antagonist pentylenetetrazole (PTZ), which evokes clonic-like seizures in fish (25). tsc2 vu242/vu242 exhibited more PTZ-induced highvelocity outbursts that began much earlier than in the controls ( Fig.…”

Section: Lack Of Tsc2 Leads To White Matter Disruption and Brainmentioning

confidence: 99%

TrkB hyperactivity contributes to brain dysconnectivity, epileptogenesis, and anxiety in zebrafish model of Tuberous Sclerosis Complex

Kedra

Banasiak

Kisielewska

et al. 2020

Proc. Natl. Acad. Sci. U.S.A.

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Tuberous Sclerosis Complex (TSC) is a rare genetic disease that manifests with early symptoms, including cortical malformations, childhood epilepsy, and TSC-associated neuropsychiatric disorders (TANDs). Cortical malformations arise during embryonic development and have been linked to childhood epilepsy before, but the underlying mechanisms of this relationship remain insufficiently understood. Zebrafish have emerged as a convenient model to study elementary neurodevelopment; however, without in-depth functional analysis, the Tsc2-deficient zebrafish line cannot be used for studies of TANDs or new drug screening. In this study, we found that the lack of Tsc2 in zebrafish resulted in heterotopias and hyperactivation of the mTorC1 pathway in pallial regions, which are homologous to the mammalian cortex. We observed commissural thinning that was responsible for brain dysconnectivity, recapitulating TSC pathology in human patients. The lack of Tsc2 also delayed axonal development and caused aberrant tract fasciculation, corresponding to the abnormal expression of genes involved in axon navigation. The mutants underwent epileptogenesis that resulted in nonmotor seizures and exhibited increased anxiety-like behavior. We further mapped discrete parameters of locomotor activity to epilepsy-like and anxiety-like behaviors, which were rescued by reducing tyrosine receptor kinase B (TrkB) signaling. Moreover, in contrast to treatment with vigabatrin and rapamycin, TrkB inhibition rescued brain dysconnectivity and anxiety-like behavior. These data reveal that commissural thinning results in the aberrant regulation of anxiety, providing a mechanistic link between brain anatomy and human TANDs. Our findings also implicate TrkB signaling in the complex pathology of TSC and reveal a therapeutic target.

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“…Epilepsy, which affects approximately 50 million people worldwide (WHO, ), is characterized by recurrent convulsions/seizures, behavioural impairments, pathological neural activity and endocrine dysfunction (Andrea Galimberti et al, ; Zhang and Liu, ; Green et al, ; Engel, ). Epilepsy can be modelled in larval and adult zebrafish (primarily by administration of convulsant drugs and genetic modifications) and evaluated by various behavioural and physiological endpoints (Wong et al, ; Desmond et al, ; Cunliffe, ). Characteristic behaviours for epilepsy‐like states in adult zebrafish are hyperactivity, erratic swimming, loss of body posture, spasm‐like corkscrew swimming (Desmond et al, ) and electrical discharges in the CNS (Baraban et al, ; Zdebik et al, ).…”

Section: Zebrafish Models Of Major Cns Disordersmentioning

confidence: 99%

“…Epilepsy can be modelled in larval and adult zebrafish (primarily by administration of convulsant drugs and genetic modifications) and evaluated by various behavioural and physiological endpoints (Wong et al, ; Desmond et al, ; Cunliffe, ). Characteristic behaviours for epilepsy‐like states in adult zebrafish are hyperactivity, erratic swimming, loss of body posture, spasm‐like corkscrew swimming (Desmond et al, ) and electrical discharges in the CNS (Baraban et al, ; Zdebik et al, ). Experimental seizures in zebrafish can be induced by acute caffeine (250 mg·L −1 ), pentylenetetrazole (PTZ, 2.5 g·L −1 ) and picrotoxin (100 mg·L −1 ), causing hyperactivity, circular/corkscrew swimming, spasms and elevated whole‐body cortisol levels (Wong et al, ).…”

Section: Zebrafish Models Of Major Cns Disordersmentioning

confidence: 99%

Zebrafish models in neuropsychopharmacology and CNS drug discovery

Khan

Collier

Meshalkina

et al. 2017

British J Pharmacology

152

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Despite the high prevalence of neuropsychiatric disorders, their aetiology and molecular mechanisms remain poorly understood. The zebrafish (Danio rerio) is increasingly utilized as a powerful animal model in neuropharmacology research and in vivo drug screening. Collectively, this makes zebrafish a useful tool for drug discovery and the identification of disordered molecular pathways. Here, we discuss zebrafish models of selected human neuropsychiatric disorders and drug-induced phenotypes. As well as covering a broad range of brain disorders (from anxiety and psychoses to neurodegeneration), we also summarize recent developments in zebrafish genetics and small molecule screening, which markedly enhance the disease modelling and the discovery of novel drug targets.

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Assessing Epilepsy-Related Behavioral Phenotypes in Adult Zebrafish

Cited by 10 publications

References 27 publications

Zebrafish as a Model for Epilepsy-Induced Cognitive Dysfunction: A Pharmacological, Biochemical and Behavioral Approach

Zebrafish as a Model for Epilepsy-Induced Cognitive Dysfunction: A Pharmacological, Biochemical and Behavioral Approach

TrkB hyperactivity contributes to brain dysconnectivity, epileptogenesis, and anxiety in zebrafish model of Tuberous Sclerosis Complex

Zebrafish models in neuropsychopharmacology and CNS drug discovery

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