An animal model to study new treatments against epilepsy
FUSAL/DICYT The University of Salamanca has an animal model to study epilepsy. The hamster called GASH: Sal (Genetic Audiogenic Seizure Hamster: Salamanca) presents seizures of genetic origin similar to those suffered by epileptic humans. Morphological, genetic, pharmacological and physiological studies confirm that the model is valid and useful to test any developing antiepileptic therapy.
In other animal models it is necessary to induce seizures by using chemical products or electrical stimulation, but in this case, they are triggered simply when the rodent hears a sound. The researchers believe that this option is much more reliable. In addition, their seizures are deep and extensive, so that they allow to analyze in detail the reaction of the animal to possible treatments against epilepsy.
"We have been working on this model for 10 years and we have characterized in depth considering several characteristics such as its response to antiepileptic drugs and its behavior during epileptic crises. We have also conducted studies on the histology of the nervous system," says Dolores López, a researcher at the Institute of Neurosciences of Castilla y León (INCYL) of the University of Salamanca.
This is an old research. "It started in the 70's in a curious way. A group of researchers from the University of Valladolid realized that these animals suffered convulsive episodes when there was a shrill noise in the room where they were kept," recalls Luis Muñoz, head of the Animal Experimentation Service of the University of Salamanca.
From 2005, the work of Luis Muñoz allowed to recover and characterize this strain of animals and now "the idea is to preserve this line for the scientific community as an experimental model for testing new drugs so that they might be validated for its use in humans.
Bearing this objective in mind, a new project is now trying to find out the genes responsible for these animals audiogenic epilepsy. Researchers have been able to develop this work thanks to the Proof of Concept call of the General Foundation of the University of Salamanca, within the TCUE program of the Regional Government of Castilla y León, co-financed with FEDER funds.
Discovering those keys genes will be crucial to progress in therapeutic research against epilepsy, for example, to develop a transgenic mouse susceptible to seizures. In addition, having introduced specific genetic modifications, this animal would be patentable.
"We have employed indirect strategies to analyze the hamster genome, such as performing a comparative analysis of the genes of our strain and the golden hamsters as control, by using the NovaSeq 6000 sequencing technology from Illumina, which uses a gene database of mice to compare ", explains Dolores López.
Tow key genes
After a bioinformatic analysis, the results indicate that there are two genes that differentiate the GASH:Sal model from the control mice, so "we are performing the sequencing of these genes to explore their connection with the epileptic seizures."
In addition, scientists want to see what differences there are between the proteins coded by these genes. To do this, "we are carrying out a comparative analysis that consists of separating all the proteins by means of a technique called differential bidimensional electrophoresis and then we carry out an analysis by mass spectrometry". All this will confirm the differences between the hamsters of the strain that presents seizures and the animals that serve as a control.
In addition, one of the objectives of scientists is to ensure the seizure strain conservation and for this purpose, they intend to preserve the genetic heritage of these animals by freezing embryos.
On the other hand, according to Ricardo José Gómez Nieto, also an INCYL scientist, from this project are derived other studies that use computerized systems of analysis and three-dimensional reconstruction, in particular, a software known as NeuroLucida. "These studies try to determine the morphological and functional alterations in the nuclei of the auditory pathway that could contribute to the susceptibility of our rodent model to epileptic seizures," he says.
In short, "the idea is to characterize them completely," says Dolores López. "If we know which gene sequences produce this susceptibility, the next step is to make a transgenic mouse, because it is easier to use and, having introduced these genes, we could patent it", summarizes.