Molecule shields brain from seizure

BROWN (US) — The presence of a molecule in the brain following an epileptic seizure appears to exist solely to protect the brain from further seizures down the road.

Putrescine is one in a family of molecules called “polyamines” that are present throughout the body to mediate crucial functions such as cell division. Why they surge in the brain after seizures isn’t understood.

Neuroscientists traced their activity in the brains of seizure-laden tadpoles and found that putrescine ultimately converts into the neurotransmitter GABA, known to calm brain activity.

When a seizure was forced in tadpoles, researchers found that the putrescine produced in a first wave of seizures helped tadpoles hold out longer against a second wave of induced seizures.

Further research could ultimately produce a drug that targets the process, potentially helping young children with epilepsy, says Carlos Aizenman, assistant professor of neuroscience at Brown University.

Tadpoles and toddlers aren’t much alike, but this basic aspect of their brain chemistry is.

“Overall, the findings presented in this study may have important therapeutic implications. We describe a novel role for polyamine metabolism that results in a protective effect on seizures induced in developing animals.”

The study is published in the journal Nature.

The fact that priming tadpoles with a seizure led to them being 25 percent more resistant to a subsequent seizure four hours later was “puzzling,” says Aizenman, who conducted about a dozen more experiments before solving the mystery.

First the team hindered polyamine synthesis altogether and found that not only did the protection against seizures disappear, but it also left the tadpoles even more vulnerable to seizures.

Then they interrupted the conversion of putrescine into other polyamines and found that this step enhanced the protection, indicating that putrescine was the beneficial member of the family.

Going with those results, they administered putrescine directly to the tadpoles and found that it took 65 percent longer to induce a seizure than in tadpoles that didn’t get a dose of putrescine.

The protective effect occurs after putrescine is metabolized, with at least one intermediary step, into GABA, and GABA receptors are activated in brain cells.

“Potentially by manipulating this pathway we may be able to harness an ongoing protective effect against seizures,” Aizenman says. “However I should caution that this is basic research and it is premature to predict how well this would translate into the clinic.”

In the meantime, the research may also help explain a bit more about young brains in general, Aizenman says.

“Our findings may also tell us how normal brains, especially developing brains, may regulate their overall levels of activity and maybe keep a type of regulatory check on brain activity levels.”

The research was funded in part by the American Heart Association and the National Institutes of Health.

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