Epilepsy research methods update: Understanding the causes of epileptic seizures and identifying new treatments using non-mammalian model organisms

Cunliffe, Vincent T.; Baines, Richard A.; Giachello, Carlo N.G.; Lin, Wei‐Hsiang; Morgan, Alan; Reuber, Markus; Russell, Claire; Walker, Matthew C.; Williams, Robin S.B.

doi:10.1016/j.seizure.2014.09.018

Cited by 65 publications

(83 citation statements)

References 89 publications

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“…Several decades ago the development of genetic and experimental murine and rodent epilepsy models marginalized interest in the baboon model due to their lower cost, wider availability, miniaturization of equipment, and ethical concerns. And currently, ASM screening is utilizing even smaller and less‐expensive animal models, including zebra fish, Caenorhabiditis elegans , and Drosophila melanogaster . Alternatively, canine epilepsy models can assess long‐term focal seizure detection and neurostimulation as well as studies on the mechanisms underlying genetic generalized epilepsy with myoclonus and photosensitivity and the progressive myoclonic epilepsy associated with Lafora disease .…”

Section: Discussionmentioning

confidence: 99%

Epilepsy in nonhuman primates

Croll¹,

Szabó

Abou‐Madi

et al. 2019

Epilepsia

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Objectives Nonhuman primates (NHPs) are model organisms for understanding the pathophysiology and treatment of epilepsy in humans, while data from human patients informs the diagnosis and treatment of NHP with seizures and epilepsy. We reviewed the literature and surveyed veterinarians at zoos and NHP research centers to (a) better define the range of seizures and epilepsy in NHP, (b) understand how NHPs can inform our knowledge of the pathophysiology and treatment of epilepsy in humans, and (c) identify gaps of knowledge and develop more effective guidelines to treat seizures and epilepsy in NHP. Methods We searched PrimateLit, PubMed, and Google Scholar for studies on experimental models of epilepsy in NHPs and on naturally occurring seizures and epilepsy in NHPs in captivity. In addition, we created a survey to assess methods to diagnose and treat epilepsy in NHPs. This survey was sent to 41 veterinarians at major international zoos and research facilities with NHP populations to study seizure phenomenology, diagnostic criteria for seizures and epilepsy, etiology, and antiseizure therapies in NHPs. Results We summarize the data from experimental and natural models of epilepsy in NHPs and case reports of epilepsy of unknown origin in captive primates. In addition, we present survey data collected from veterinarians at eight zoos and one research facility. Experimental data from NHP epilepsy models is abundant, whereas data from primates who develop epilepsy in the wild or in zoos is very limited, constraining our ability to advance evidence‐based medicine. Significance Characterization of seizure or epilepsy models in NHPs will provide insights into mechanisms and new therapies that cannot be addressed by other animal models. NHP research will better inform species‐specific diagnoses and outcomes.

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Section: Discussionmentioning

confidence: 99%

Epilepsy in nonhuman primates

Croll¹,

Szabó

Abou‐Madi

et al. 2019

Epilepsia

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“…In this review we shall critically assess the most notable and recently published models, disease mechanisms and therapeutic testing utilising zebrafish (Table 1) and endeavour to stimulate further research in this important area. Although overlaps exist between epilepsy and neurodegenerative disease, we will refrain from reviewing zebrafish models of epilepsy in detail here as this disorder has been recently reviewed [1,6], along with zebrafish models of mitochondrial disease [7,8], metabolic disease [9] and neurological disorders [1, 10, 11].…”

Section: Introductionmentioning

confidence: 99%

New Zebrafish Models of Neurodegeneration

Martín-Jiménez

Campanella

Russell

2015

Curr Neurol Neurosci Rep

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In modern biomedicine the increasing need to develop experimental models to further our understanding of disease conditions and delineate innovative treatments has found in the zebrafish (Danio rerio) an experimental model, and indeed a valuable asset, to close the gap between in vitro and in vivo assays. Translation of ideas at a faster pace is vital in the field of neurodegeneration, with the attempt to slow or prevent the dramatic impact on society's welfare being an essential priority. Our research group has pioneered the use of zebrafish to contribute to the quest for faster and improved understanding and treatment of neurodegeneration in concert with, and inspired by, many others who have primed the study of the zebrafish to understand and search for a cure for disorders of the nervous system. Aware of the many advantages this vertebrate model holds, here we present an update on the recent zebrafish models available to study neurodegeneration with the goal of stimulating further interest and increasing the number of diseases and applications for which they can be exploited.We shall do so by citing and commenting on recent break-throughs made possible via zebrafish, highlighting their benefits for the testing of therapeutics and dissecting of disease mechanisms.

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“…Genetic mutations play an important etiological role in the development of epilepsy in hereditary cases of this disease (5–10). However, the mechanism of seizures in a significant proportion of patients remains unexplained.…”

Section: Mechanism Of Idiopathic Epilepsy Is Not Clearmentioning

confidence: 99%

Pore-Forming Proteins as Mediators of Novel Epigenetic Mechanism of Epilepsy

et al. 2017

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Epilepsy is a disorder of the brain characterized by an enduring predisposition to generate epileptic seizures. In the last two decades, numerous gene defects underlying different forms of epilepsy have been identified with most of these genes encoding ion channel proteins. Despite these developments, the etiology of majority of non-familial epilepsies has no known associated genetic mutations and cannot be explained by defects in identified ion channels alone. We hypothesize that de novo formation of ion channels by naturally unfolded proteins (NUPs) increases neuronal excitability. Altered ionic homeostasis may initiate/contribute to cellular cascades related to epileptogenesis in susceptible individuals. Here, we consider two small proteins, namely, α-synuclein and stefin B, as prototypical candidates to illustrate the underlying mechanism(s). Previous work points to an association between epilepsy and α-synuclein or stefin B, but the mechanism(s) underlying such association remains elusive. We review the evidence to link the structure–function of these proteins with disease processes. Epigenetic mechanisms unrelated to altered DNA sequence(s) that may affect epileptogenesis include transcriptional or posttranscriptional regulation. Such epigenetic mechanisms or their combination(s) enhance the levels of these proteins and as a result the ability to form annular structures, which upon incorporation into membrane form novel ion channels and disturb intracellular ion homeostasis. Alternative epigenetic mechanisms may change amyloidogenic proteins by posttranslational modifications, thereby increasing their propensity to form channels. Further research elucidating the details about the formation of ion channels through these mechanisms and their role in epileptogenesis may define new molecular targets and guide the development of new drug targets.

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Epilepsy research methods update: Understanding the causes of epileptic seizures and identifying new treatments using non-mammalian model organisms

Cited by 65 publications

References 89 publications

Epilepsy in nonhuman primates

Epilepsy in nonhuman primates

New Zebrafish Models of Neurodegeneration

Pore-Forming Proteins as Mediators of Novel Epigenetic Mechanism of Epilepsy

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