Genetic Changes that Cause Loss of a Certain Type of Memory Can Also Protect Against Epilepsy
A new biological mechanism that damages only a specific type of memory can provide protection against epilepsy according to a study published in the scientific journal Cerebral Cortex.
The biological pathway involves a genetic modification in a protein called eEF2K, which regulates the expression of other proteins. According to the authors, the eEF2K protein could be a potential new target for antiepileptic drugs (AEDs).
The findings came by chance while the team of international researchers were trying to isolate molecular components involved in long-term memory whilst working on learning and memory.
Using a mouse model, the researchers made a molecular change to the eEF2K gene, which resulted in the complete lack of the protein that the gene encodes for. They then tested the mice behaviourally to assess their memory.
They saw that the lack of eEF2K protein caused damage to a specific type of memory called context memory, whilst keeping consolidation of other types of memory intact.
When they further analysed the brains of these animals, the researchers found that a certain part of a receptor called GABAAR and another protein called synapsin2b were over expressed. The over expression of GABAAR causes the nerve cells to be less active while the overexpression of synapsin2b causes them to be more active.
In a press release, one of the authors of the study, Elham Taha, explained: “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. 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.”
As a next step, the researchers genetically-engineered mice with epilepsy that lacked eEF2K protein, to find out if eEF2K down-regulation decreases seizure activity. EEG tests revealed that these animals did not have any seizures.
The scientists also sought to find out whether chemically (rather then genetically) inhibiting the eEF2K protein would have the same effect. They gave mice with epilepsy (that had low levels of synapsin2b) a substance that inhibits the expression of eEF2K protein. They noticed that the mice did not experience any seizures during the following week.
For both the genetic and chemical methods, when the researchers looked at the expression of synapsin2b they saw that the levels had been brought to normal as a result of eEF2K absence/inhibition.
In the future, the researchers want to find ways to block the expression of eEF2K in only certain nerve cells “in order to improve our understanding of the basis of epilepsy and to create new possibilities for treating the disease.”
Author: Dr Özge Özkaya
Click here for more articles about brain science including genetics.