Professor Russell Ferland, who has a Ph.D. in neuroscience, and biology graduate student Dominick Papandrea comprise one of the many research teams conducting unprecedented research in the Center for Biotechnology and Interdisciplinary Studies. The most recent developments have recently been published in Experimental Neurology.
Over the years, many researchers have attempted to reveal the cause of a medical phenomenon that is seen when, for example, two children are brought to the emergency room due to febrile seizures, which can occur when they reach abnormally high temperatures during a fever. One of those children may grow up and have no complications for the rest of his life. However, like many documented cases, the other may suffer a series of seizures 15 or 20 years later, and be diagnosed with epilepsy.
Research conducted by Ferland’s team indicates that, based on genetic predisposition, those who experience full-blown epilepsy could have undergone a long-lasting change in the brain onset from an initial seizure, which makes them much more susceptible to developing epilepsy. This permanent change is known as epileptogenesis.
Exactly what that permanent change is and its genetic basis are key to gaining a much more comprehensive understanding of how and why epilepsy develops. After spending years gathering data, Ferland’s team is attempting to determine the genes that are involved in both epilepsy and epileptogenesis.
The discovery, as Ferland has previously mentioned, could help treat epilepsy and possibly find a cure.
Years ago, Ferland’s team began by using mice animal models. They started by analyzing two general types of strains of mice, one of which displayed seizure predispositions.
These mice had an initially high resistance to seizures that gradually decreased with each seizure over an eight-day period. Ferland’s team analyzed this by mapping the seizure threshold level of the mice.
The mice had a month-long resting period, allowing researchers to observe the long lasting effects of the initial seizures. However, results showed that the lowered resistance rate acquired as a consequence of the initial eight-day testing trail was changed.
According to RPI News, “These changes in seizure behavior show us that a different portion of the brain is being changed and activated during the rest period,” Ferland said.
He and his research team then began working to determine what change in the brain was induced during the initial seizures. “Those initial seizures created a lasting change in the brain.”
In addition to studying the phenotypes of these mice to determine the genes involved in epileptogensis, Ferland’s team is also mapping changes in the brains of the tested mice. During the month-long rest period, Papandrea noticed that a different portion of the brain is activated during the change period than the portion activated during seizures. These results could give clues to where the changes that cause epileptogenesis to occur.
However, while working with several other strains of mice and examining the type and severity of their seizures, the researchers found that one strain had a low initial resistance that remained unchanged during the eight-day period and after the month-long resting period.
This constant low-resistance was about the same as the lowest resistance of the first strain after eight days. In addition, unlike in the first strain of mice, the type of seizure did not change after the trial and resting period.
To test the genetic basis of the thresholds, the team used a hybrid mouse with half of its genetic material from each of the two strands discussed.
The hybrid had a high initial resistance to seizures that decreased, but no change in the type or severity of the seizure, a perfect hybrid of phenotypes for the crossed strains.
Now that the team has its basic model and type of strains for research, they will continue to breed generations of mice in such a way that they can hone in on the genes gradually with each generation until they find a very small region of genes to work with, in hopes of learning more about how these genes play a role in epileptogenesis and epilepsy.
Ferland commented upon how much the experiment’s results rely on tracing the phenotypes and genes of the hybrid generations: “It could be more than one gene. We don’t know much about the genetic basis at this point. “There could be multiple genes involved with epileptogenesis, which is very likely but will make it much harder to understand how the genes work to cause epileptogensis.
“We could narrow the potential gene pool down to 50 genes, which would be very hard to work with, or we could get really lucky and find one gene or one coupling of genes that causes these changes in the brain,” he continued. “It all depends on how lucky we get.
Upon being asked to estimate a time frame before the team gets a reasonably sized gene pool narrowed down, Papandrea laughed. “It will take years to narrow down which genes are involved. I hope I’m not still here when were done.”
