Is a micro-gene a factor in epileptic seizures?
Seizures in epilepsy can be caused by genetic factors or they can be triggered by injury. While we know that all brains are capable of generating seizures we do not know why some brains do not develop them. A good example is epilepsy that develops as a result of an ischemic stroke. Only some of the people who have an ischemic stroke will develop epilepsy so it has long been conjectured that there are also other factors at play.
Researchers at the Hebrew University in Jerusalem believe they may have found one of these factors in the form of a micro-gene.
The research, which has been published in the journal Proceedings of the National Academy of Sciences, 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.
Prof. Hermona Soreq and her team tested their hypothesis through a 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 the 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.
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.
“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.