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Although this new research is not yet transferable to humans, Venø and Kjems are involved in a five-year project, where the role of microRNA in epilepsy is being examined for future treatments.

New insight into epilepsy

Research on mice shows that microRNA-128 has a direct effect on the musculoskeletal system. When it is increased, neuron activity is lowered — reducing uncontrolled movements in connection with epilepsy or Parkinson’s. When decreased, microRNA-128 boosts neuron activity.

Jørgen Kjems and Morten Trillingsgaard Venø, Department of Molecular Biology and Genetics and the Interdisciplinary Nanoscience Centre (iNANO), Aarhus University, contribute to an article on microRNA-128 just published in Science.

In experiments on mice, it was possible to control the amount of microRNA-128 in specific neurons that react to the signal substance dopamine.

“If microRNA-128 is kept low in neonatal mice, it results in a a higher level of activity, the mice move more, develop epilepsy and finally die of seizures.”

Morten T. Venø, postdoc, Department of Molecular Biology and Genetics, the Interdisciplinary Nanoscience Centre (iNANO), Aarhus University.

Morten T. Venø, postdoc, worked with project leader Anne Schaefer on an advanced technology to make it possible to see microRNA actually bind to mRNA. They worked with genetically modified mice to produce a particular type of Ago protein in the brain's neurons. Ago proteins bind to both microRNA and mRNA at the same time, which suggests that mRNAs are broken down, or that their 'translation' into protein is somehow interfered with.

This particular Ago protein, together with the RNA that is bound to it, can be purified from the brain tissue of mice with the help of an antibody. The researchers were therefore able to determine where different microRNA in the neurons bind.

MicroRNA-128 turned out to be the microRNA that controls the greatest number of mRNAs in the brains of the mice - more specifically in the neurons!

Together with his former supervisor Jørgen Kjems, the young researcher has continued to collaborate with Anne Schaefer on microRNA-128 and its function in neurons.

Experiments on mice show that you can check the amount of microRNA-128 in neurons that respond to dopamine, and thus also check how it affects a wide variety of gene expression in these neurons, which results in an altered activation of the neurons.

"A large volume of microRNA-128 results in a lower neuron activity and can help to hamper the degree of activation in the musculoskeletal system. Such a strong reaction to a change in the microRNA level is rarely seen.

The reason for the intense effect of the microRNA 128 reduction in neurons must probably be due to the fact that microRNA 128 regulates a lot of mRNAs (and, thus, many gene expressions)," explains Venø.

The new research is not yet transferable to humans, but Morten T. Venø and Jørgen Kjems are involved in a five-year EU project, where the role of microRNA in epilepsy is being examined with a view to future treatment.

In addition to microRNA 128, microRNA 134 also has an impact on epilepsy, particularly under the microscope.

Abstract
The control of motor behavior in animals and humans requires constant adaptation of neuronal networks to signals of various types and strengths. We found that microRNA-128 (miR-128), which is expressed in adult neurons, regulates motor behavior by modulating neuronal signaling networks and excitability. miR-128 governs motor activity by suppressing the expression of various ion channels and signaling components of the extracellular signal–regulated kinase ERK2 network that regulate neuronal excitability. In mice, a reduction of miR-128 expression in postnatal neurons causes increased motor activity and fatal epilepsy. Overexpression of miR-128 attenuates neuronal responsiveness, suppresses motor activity, and alleviates motor abnormalities associated with Parkinson’s–like disease and seizures in mice. These data suggest a therapeutic potential for miR-128 in the treatment of epilepsy and movement disorders.

Editor's Summary
Not Too Much, Not Too Little
The microRNA miR128 is expressed in brain neurons of the mouse. Lek Tan et al. (p. 1254) now find that miR128 is crucial to stable brain function. Mice deficient in miR128 developed hyperactivity and were susceptible to fatal seizures, whereas overexpression of miR128 correlated with reduced motor activity and reduced susceptibility to proconvulsive drugs. Experiments using ex vivo–isolated adult brain tissues suggested that miR-128 controlled motor activity by governing the signaling network that determines the intrinsic excitability and signal responsiveness of neurons.

Aarhus University has fourteen basic research centres supported by the Danish National Research Foundation. http://www.au.dk/en/