Student-conducted research at the University's Institute for Brain Science revealed that synthesis of the molecule putrescine during a seizure can protect the brain from recurrent episodes. Further research on the physiological effects of putrescine and other polyamines could ultimately lead to a treatment for epilepsy.
The study concluded that putrescine is converted into gamma-aminobutryic acid — the primary inhibitory neurotransmitter that calms brain activity — and that a surge of GABA during the preliminary seizure helps prevent later episodes, said Mark Bell GS, who conducted the majority of the experiments. The research team found that it took 65 percent longer to induce a seizure in tadpoles that had been given a dose of putrescine compared to those that were not administered the polyamine, according to a University press release.
"If you block polyamine synthesis around the time of the seizure and then induce a seizure four hours later, there is no protective effect," said Hannah Johnson '11, a student involved in the research. "It was already known that there is a spike in putrescine after a seizure, but no one knew before if it was helping or causing more cell damages."
"We came across the idea of polyamines in general by giving the tadpole a seizure, waiting around four hours and giving it another seizure. The animal was more resistant the second time," Bell said. "This was a very curious find, and we wanted to explore it."
The research team proceeded to identify beneficial polyamines by blocking several different ones from synthesis during the first seizure and found that the animal "did worse four hours later" when the polyamines were removed from the process, according to Johnson. Ultimately, the team found that putrescine was the main protective molecule responsible for limiting the severity of a seizure.
"We were hoping to see that more complex polyamines have an effect on seizures," said Assistant Professor of Neuroscience Carlos Aizenman. "Putrescine was thought to have very little effect, but when we blocked it, we found that the simple polyamine had the biggest effect."
Aizenman, Bell and several undergraduates have been working on the epilepsy research since 2005 with funding from the National Institutes of Health, National Science Foundation and Matthew Siravo Memorial Foundation. The Institute for Brain Science has played an important role recently in the development of the seizure study and similar scientific endeavors.
"The institute helps to create an environment conducive to great work and put faculty in a good position to receive grants," said institute Associate Director John Davenport.
"The Plan for Academic Enrichment allocated seven new faculty positions to the institute, one of which was filled by Aizenman, who has directed the seizure study," Davenport said.
Since the research team has identified how the chemical works in conjunction with seizures, further research on the subject could eventually produce a drug that could control seizures in epilepsy patients. But that is a long way off, Aizenman said.
"This is still something in the early stages," he said. "If this holds up in different species, some other researchers could use the findings for a novel therapy to treat epilepsy."
Although the study has not identified treatment for epilepsy, the current findings will play an important role in future medical research.
"We have been looking to better understand the underlying mechanisms, which is obviously the first step if you want to find any kind of therapeutic implications," Johnson said.
