A small molecule called microRNA-211 protects the brain from epileptic seizures in mice, Israeli researchers have found.
Their study, “Dynamic changes in murine forebrain miR-211 expression associate with cholinergic imbalances and epileptiform activity,” appeared in the journal Proceedings of the National Academy of Sciences (PNAS).
One day 20 years ago, hundreds of Japanese children were rushed to hospital emergency rooms with epilepsy-like seizures. Their symptoms began while the kids were watching a Pokémon TV show. Doctors later attributed the seizures to five seconds of intensely bright flashing lights on the popular TV program. But why were only these few hundred children affected while thousands of other viewers were unharmed?
Hermona Soreq, a professor at Israel’s Hebrew University of Jerusalem, led a team of researchers in a quest to answer this question. Soreq thought that something in the brains of the unaffected children must have protected them, and that this mechanism must be fast-acting. She further hypothesized that these could be short RNA molecules belonging to the class of non-coding RNAs called microRNAs, which can prevent genes from expressing certain proteins.
Researchers looked specifically to the microRNA (miR)-211. To establish if it had indeed a role in epilepsy, scientists engineered a genetically modified mouse to express unusually high amounts of miR-211. The overexpression of miR-211 in the brain could be suppressed by administering the antibiotic doxycycline.
After suppressing the levels of miR-211 in the brains of transgenic mice to those found in the brains of normal mice, researchers found that, within four days, mice exhibited electrically recorded epilepsy and hypersensitivity to epilepsy-inducing compounds. These results support miR-211’s protective role against epileptic seizures in these 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,” Soreq said in a press release.
People with Alzheimer’s disease are known to carry high levels of miR-211 in their brains, which led to researchers hypothesizing that miR-211 may also exert a protective role in human brains to reduce epileptic seizures.
“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,” Soreq concluded. “In searching for the physiological mechanisms that allow some people’s brains to avoid epilepsy, we found that increased levels of micro-RNA 211 could have a protective effect.”