A sensor has been developed to monitor seizures due to epilepsy in real-time. The research team led by Hyun Teak-hwan (Chair-professor at Seoul National University), at IBS (Institute of Basic Science) Center for Nanoparticle Research, has developed a highly sensitive nanosensor that simultaneously measures changes in the concentration of potassium ion (K+) in different areas of the brain. The team also has succeeded in real-time monitoring the seizure of freely moving mice.

Epilepsy, one of the three major brain diseases, is caused by irregular excitability of brain neurons. Excited brain neurons relax by releasing potassium ions outward. However, if potassium ions in neurons cannot escape and they remain excited, seizures, and convulsions, which are the main symptoms of epilepsy, will occur.

▲ The structure of potassium ion nanosensor (Image by: IBS)

For an accurate diagnosis of brain diseases, including epilepsy, due to neuronal activity, it is necessary to track and observe changes in potassium ion concentrations in various brain regions. Seizures and convulsions due to epilepsy are so frequent that 1% of the population has them, but until now, it has been challenging to catch changes in neurons in real-time. This is because it is difficult to selectively measure the concentration change of potassium ions among various ions (potassium, sodium (Na), calcium (Ca)) that move through the ion channel of the cell membrane when the nerve cell is excited. On top of that, the concentration change of potassium ions is relatively small compared to other ions, making it more challenging to measure.

Accordingly, many studies have been conducted to develop a potassium sensor having excellent selectivity and sensitivity. However, the existing technology has a limitation in that concentration can be measured only in limited environments such as cultured neurons, brain slices, and anesthetized animals. Because movement is immediately reflected in the activity of brain neurons, a more accurate observation requires a technique that can measure activity even when freely moving.

▲ Measurement of nerve cell activity through potassium ion (Image by: IBS)

Therefore, by using nanoparticles, IBS researchers have developed a high-sensitivity nanosensor that can selectively measure changes in potassium ion concentration in mice that roam freely. The researchers first put dyes that fluoresce green when combined with potassium ions into silica nanoparticles with pores of several nanometers(nm). The surface of the nanoparticles was coated with a thin membrane that had a structure similar to that of the potassium channels in the cell membrane, selectively passing only potassium. Then, the concentration of potassium ions could be measured based on the intensity of the fluorescence of the potassium ions passing through the membrane and combining with the dye.

The researchers then injected the nanosensors into the hippocampus, amygdala, and cerebral cortex of a moving mouse, followed by electrical stimulation to the hippocampus, causing seizures, and measuring changes in potassium ion concentration. As a result, in the case of focal seizure, the concentration has increased in the order of the hippocampus, where the stimulation started, amygdala, and cerebral cortex. On the other hand, in the case of the generalized seizure, the concentration of potassium ions in three sites increased at the same time, and the duration was also increased.

▲ Analysis result of the degree of seizure using nanoparticles (Image by: IBS)

The study will contribute to understanding accurate pathogenesis of seizures, as it became possible to measure brain neuronal activity in real-time while freely moving and simultaneously monitor concentration changes in different areas of the brain. What's more, since potassium ion concentration is an indicator for monitoring the occurrence of brain diseases such as Alzheimer's disease and Parkinson's disease as well as epilepsy, the researchers hope the findings will help identify and diagnose the pathogenesis of many brain diseases caused by excessive excitability of various brain neurons.

The findings were published in Nature Nanotechnology (IF 43.341), the world's top authority in nanotechnology, on Feb 11, 1 a.m. (KST).

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