In recent years there has been a growing interest in epilepsy susceptibility genes, and approximately 13 have been identified in humans to date. Susceptibility genes do not necessarily cause epilepsy, but they render a person more likely to develop it if they are exposed to certain environmental/metabolic triggers.
Rodents are very useful in genetic studies for a number of reasons. However, although they are only used in research when absolutely necessary, and are made to suffer as little as possible, there is increasing interest amongst scientists to use models that are fundamentally simpler. These will ideally have a lower capacity to feel pain, and they will also be more economical to keep.
Dr Vincent Cunliffe and colleagues, at the University of Sheffield, are currently focusing on the zebrafish as a potential model of genetic epilepsy. Zebrafish can be bred within the laboratory very economically, and their larvae are transparent, meaning that the activity of individual brain cells can easily be observed. Zebrafish and human brains are also very similar anatomically, and both are susceptible to experimentally-induced epileptic seizures. This means that the mechanisms identified in zebrafish are likely to be relevant to human epilepsy. The team in Sheffield has already used the zebrafish to identify new anti-convulsant compounds, and it is keen to build on this work.
Dr Cunliffe has been awarded £29,979 over 12 months, for a pilot grant entitled Zebrafish genetic models of epilepsy for elucidating seizure mechanisms and identifying new therapeutics; in which he and his colleagues will create three different types of zebrafish that carry a mutation in one of three different genes. The mutations in question are the zebrafish equivalents of three known human epilepsy-susceptibility mutations, whose mechanisms in epilepsy need to be explored. If the mutations have the same effect in terms of seizure activity as the human mutations, these zebrafish models could potentially help to increase our understanding of the genetic pathways that regulate seizure susceptibility. This will hopefully lead to the identification of new treatment targets, and ultimately to the development of novel anti-epileptic drugs.