Astrocytes could be a potential new target to better treat epilepsy

A significant number of patients with epilepsy do not respond to currently available drugs. A collaboration between Japanese researchers and the Heinrich Heine University in Düsseldorf (HHU) has now addressed a type of brain cell that has so far not received much attention in the treatment of epilepsy. In the current edition of the Journal of Neuroscience, they describe that astrocytes could be a potential new target to better treat this disease.

In epileptic seizures, a large number of nerve cells in the brain are triggered excessively and in sync. This hyperactivity can lead to uncontrolled shaking of the body and lead to periods of loss of consciousness. While about two-thirds of patients respond to anti-epileptic drugs, the rest are refractory to medical treatment and show drug resistance. These patients urgently need new therapeutic strategies.

In collaboration with colleagues in Japan, Professor Christine Rose and her doctoral student Jan Meyer from the HHU Institute of Neurobiology conducted a study on the cellular mechanisms that promote the development of epilepsy. While so far most studies and anti-epileptic drugs have targeted nerve cells (neurons), this research team has focused on a class of glial cells called astrocytes.

Glial cells make up about half of all brain cells. There are different types of glial cells, which perform different functions. Astrocytes control the local environment and are responsible for ionic balance in the brain, but also play an important role in signaling between neurons.

In their recent article, the researchers show that epileptic discharges lead to an increase in the pH of astrocytes, ie their intracellular “alkalinization”. The change in pH disrupts communication within intercellular astrocyte networks. This reduced communication between astrocytes appears to exacerbate the epileptic activity of neurons.

This finding points to a new potential target for suppressing epileptogenesis at a very early stage, namely by using drugs to suppress the changes in astrocytic pH accompanying neuronal activity.

The researchers were able to confirm this option by showing that the animals receiving such drugs suffered less severely from epileptic hyperexcitability than untreated animals.

This observation is very intriguing. But it remains to be seen whether or not it can be transferred to humans. And it will be a long time before a potential drug can be developed and actually used in clinics. “

Prof. Dr. Christine Rose, Institute of Neurobiology, HHU

The research was carried out in collaboration between the HHU and three Japanese universities (Keio University and Tokyo Medical and Dental University in Tokyo, Tohoku University in Sendai) under the “Young Glia” program of the DFG-Priority Program SPP 1757 “Functional specializations of neuroglia “coordinated by Professor Rose. This program promotes collaboration between German and Japanese laboratories. In particular, it encourages and helps young scientists to carry out their own binational research projects. For example, HHU doctoral student Jan Meyer traveled to Japan, while Mariko Onodera from Tohoku University spent two periods at the Düsseldorf Institute of Neurobiology.