Epilepsy research methods update: Understanding the causes of epileptic seizures and identifying new treatments using non-mammalian model organisms
Introduction from Professor Weiping Liao, associate editor of Seizure
Years ago we made a TV program about epilepsy. Several days later, a journalist involved in making the program called me and told me that her dog had seizures. She said it was probably a complex partial seizure that manifested with staring, loss of responsiveness, and salivating. The vivid description convinced me that it was a seizure that was really similar to complex partial seizure in humans. The story attracted my attention to seizures and experiments in animals. Actually, it is almost impossible to understanding epilepsy in humans without studies on animals. Animal models provide insights into the basic anatomy and pathways of seizures, as well as the physiological and molecular mechanisms of epilepsy. More importantly, the development of modern antiepileptic drugs (AEDs) usually starts with animal model. Studies on the mechanisms of AED actions depend largely on experiments in animal, which help clinicians to manage their patients with epilepsy optimally.
My editor’s choice from this issue of Seizure by Vincent T Cunliffe et al. extends our vision of experiments in animals from mammalian models to non-mammalian model organisms, ranging from vertebrate zebrafish to unicellular social amoeba (1). Whilst the social amoeba Dictyostelium discoideum lacks a nervous system and consequently has no physiological equivalent of an epileptic seizure, the simplicity of this organism offers great advantages for elucidating biochemical mechanisms of drug action. By contrast, the roundworm Caenorhabditis elegans, fruit fly Drosophila melanogaster and zebrafish Danio rerio have nervous systems that exhibit behaviours which are equivalent to epileptic seizures in humans. In Caenorhabditis elegans, the ~1mm-long metazoan worm with just 302 neurons, a mutated lis1 gene causes an animal form of lissencephaly associated with repetitive convulsions when worms are exposed to an GABA antagonist. The anatomical and physiological simplicity of such organisms, together with their ease of maintenance, help research efforts to understand disease mechanisms.
Besides the advantages of relative ease and simplicity, extension of experiments from mammalian model to non-mammalian model will provide unique insight into the mechanism of seizures and epilepsies. What anatomic structures are involved in the ictogenesis of complex partial seizure? What is the physiological and molecular basis of absence seizure? Answers may be expected from comparative analyses of the differences in seizure behaviors of species, whose nervous systems differ in structural, physiological and molecular aspects.
I hope this publication will allow more clinicians and researchers to understand the potential of non-mammalian animal models and “be a sprat to catch a whale” in this field.
 Cunliffe V. et al. Epilepsy Research Methods Update: Understanding the causes of epileptic seizures and identifying new treatments using non-mammalian model organisms. Seizure 2014;24:44-51.