The forced elimination of a protein, called eEF2K, may affect the brain’s ability to draw on certain memories, but that lack may also protect against epileptic seizures, according to research published in the journal Cerebral Cortex. The finding may provide a new target for therapies aiming to protect the brain against epilepsy.
The study, “eEF2K/eEF2 Pathway Controls The Excitation/Inhibition Balance And Susceptibility To Epileptic Seizures,” was conducted while researchers were studying the role of eEF2K in a certain type of memory in mice.
eEF2K is a type of protein that controls the production of other proteins in cells. Researchers observed that mice lacking the gene that encodes this protein had difficulties in producing what is called context memory, although other types of memory appeared unaffected.
They also found that, in the absence of eEF2K, mice brains had increased levels of two proteins, GABAA receptor and synapsin2b, compared to normal mice. GABAA receptors work by inhibiting neuronal activity and help to balance the activation of neurons (over-activation causes neuronal damage and loss), whereas synapsin2b works by stimulating neuronal activity. The increased levels of both proteins resulted in a change in the balance of neuronal activity and inactivity in the brain. These results also suggested to researchers that eEF2K, and its impact on GABAA receptor and synapsin2b expression, may be of relevance to epilepsy.
“We realized that, surprisingly, the change in the general translation control element, eEF2K, changes the excitation/inhibition ratio in a specific area of the brain,” Elham Taha, one of the study’s authors, said in a news release. “This area as well as the molecules whose expression changed are associated with epilepsy. For example, mutation in synapsin2b in humans or a decline in its expression may lead to epilepsy.”
To test whether the lack of eEF2K could protect mice from seizures, researchers eliminated the eEF2K gene in a mouse model of epilepsy. As expected, mice without eEF2K did not have epileptic seizures. Similar results were observed when the team inhibited eEF2K, rather than eliminating it, using a chemical compound that blocks the production of this protein. These mice also did not have seizures in the following week. In both cases, levels of synapsin2b returned to normal after eEF2K was removed or its production blocked.
“From a clinical perspective, our results identify eEF2K as a potential novel target for antiepileptic drugs, since pharmacological and genetic inhibition of eEF2K can revert the epileptic [behavior] in a mouse model of human epilepsy,” the researchers concluded.
