Astrocytes found to play a key role in epileptic neuronal hyperactivity

Epilepsy, where patients suffer from unexpected seizures, affects about 1% of the population. These seizures often involve repetitive and excessive firing of neurons, the trigger behind which is still poorly understood.

Now, researchers at Tohoku University have monitored astrocyte activity using fluorescent calcium sensors, discovering that astrocyte activity begins about 20 seconds before the onset of epileptic neuronal hyperactivity. This suggests that astrocytes play an important role in triggering seizures by facilitating over-driving of neural circuitry.

The findings were detailed in the journal Glia on April 9, 2024.

Astrocytes are non-glial cells that occupy almost half of the brain. They have been shown to control the local ionic and metabotropic environment in the brain. However, since they do not exhibit electrical activity that can be easily monitored, their role in brain function has been largely neglected. Fluorescent sensor proteins are changing this, revealing more about the fascinating activity of astrocytes.

“Astrocytes appear to have a key role in controlling the state of neuronal activity and synaptic plasticity in both normal and pathophysiological conditions,” says Professor Ko Matsui of the Hypernetwork Brain Physiology Laboratory at Tohoku University, who led the research.Therefore, astrocytes could be considered as a new therapeutic target for the treatment of epilepsy.”

When brain tissue comes into contact with metals such as copper, it is known to cause inflammation that leads to acute symptomatic seizures, which occur several times a day in mice. Matsui and his team observed these events, where they discovered that astrocyte activity can be the trigger for neuronal hyperactivity. Astrocytes can also be activated by low-amplitude direct current stimulation. The researchers observed that such stimulation caused a strong increase in astrocyte calcium, which was followed by an episode of epileptic neuronal hyperactivity. When astrocyte metabolic activity was blocked by application of fluorocitrate, the magnitude of epileptic neuronal hyperactivity was significantly reduced. All this points to the fact that astrocytes have the ability to control neuronal activity.

Study lead researcher Shun Araki emphasizes that with the right guidance, astrocyte functions could be harnessed to treat a range of neurological conditions. This includes not only epilepsy but also the potential enhancement of cognitive abilities beyond physical limitations.