Epilepsy affects tens of millions of people worldwide, but the causes of epileptic seizures remain largely unknown. New research may have found a micro-gene that explains why some brains develop epileptic seizures while others do not.
Epilepsy is a neurological disease that affects more than 5 million people in the United States, including children and adults. Worldwide, the number of people affected by epilepsy is as high as 50 million.
The condition manifests itself through recurrent seizures, which can sometimes be accompanied by a temporary loss of consciousness or convulsions.
These seizures can have genetic causes or can be triggered by different kinds of neural injury. All brains are prone to generating seizures, but the reasons why some brains do not develop them remain unknown.
For instance, although epilepsy can be developed as a result of having an ischemic stroke, only some of the people who have this type of stroke will go on to develop the condition. This suggests that there are other factors at play.
New research, published in the journal Proceedings of the National Academy of Sciences, may have found one of these factors in the form of a micro-gene.
Prof. Hermona Soreq, from the Hebrew University of Jerusalem in Israel, started out from the hypothesis that healthy brains do not have seizures when exposed to flashing lights or other triggers because of so-called short RNAs, otherwise known as rapidly inducible microRNAs.
MicroRNAs are a class of RNA – that is, one of the macromolecules needed for all forms of life, together with DNA and proteins – that have the ability to suppress the genetic expression of certain proteins.
To test their hypothesis, Soreq and her team genetically designed a type of mouse that produces very large amounts of a microRNA called miR-211.
The overexpression of miR-211 taking place in the mice’s forebrain was engineered in such a way that it could be lowered with the antibiotic doxycycline.
Soreq, along with colleagues at Ben-Gurion University of the Negev in Israel and Dalhousie University in Canada, managed to suppress the excess of miR-211 in the transgenic mice by using doxycycline, which brought the levels to normal.
After 4 days, they recorded the mice’s brain activity using electrocorticography. They found that the mice reacted to the miR-211-suppressing doxycycline by having nonconvulsive seizures, as well as by accumulating miR-134 in the forebrain.
Previous studies have suggested that miR-134 might be responsible for epileptic seizures.
The new study revealed that once they had their levels of miR-211 lowered, the mice showed signs of epilepsy and a propensity for convulsions. They displayed a hypersensitivity to compounds that induce epilepsy, such as the miR-134.
This suggests that miR-211 has a neuroprotective role and is key in preventing epileptic seizures in genetically modified mice.
“Dynamic changes in the amount of miR-211 in the forebrains of these mice shifted the threshold for spontaneous and pharmacologically induced seizures, alongside changes in the cholinergic pathway genes,” Prof. Soreq explains.
As the authors note, previous studies have shown that miR-211 is high in people with Alzheimer’s disease who are also at a higher risk of developing epilepsy. Therefore, the researchers believe that high levels of miR-211 may have the same protective effect in humans.
“It is important to discover how only some people’s brains present a susceptibility to seizures, while others do not, even when subjected to these same stressors. In searching for the physiological mechanisms that allow some people’s brains to avoid epilepsy, we found that increased levels of microRNA 211 could have a protective effect.”
Prof. Hermona Soreq
The scientists hope that their discovery will help the medical research community to develop new treatments for epilepsy. Such therapies might work by raising the levels of miR-211 in human brains.