Role of Impaired Astrocyte Gap Junction Coupling in Epileptogenesis

The gap-junction-coupled astroglial network plays a central role in the regulation of neuronal activity and synchronisation, but its involvement in the pathogenesis of neuronal diseases is not yet understood. Here, we present the current state of knowledge about the impact of impaired glial coupling in the development and progression of epilepsy and discuss whether astrocytes represent alternative therapeutic targets. We focus mainly on temporal lobe epilepsy (TLE), which is the most common form of epilepsy in adults and is characterised by high therapy resistance. Functional data from TLE patients and corresponding experimental models point to a complete loss of astrocytic coupling, but preservation of the gap junction forming proteins connexin43 and connexin30 in hippocampal sclerosis. Several studies further indicate that astrocyte uncoupling is a causal event in the initiation of TLE, as it occurs very early in epileptogenesis, clearly preceding dysfunctional changes in neurons. However, more research is needed to fully understand the role of gap junction channels in epilepsy and to develop safe and effective therapeutic strategies targeting astrocytes.

Automated summary

The gap-junction-coupled astroglial network is essential for regulating neuronal activity and synchronization, but its role in the pathogenesis of neuronal diseases is still unclear. This paper summarizes the current knowledge about the impact of impaired glial coupling in epilepsy and discusses the potential of astrocytes as therapeutic targets. It focuses on temporal lobe epilepsy (TLE), the most common form of epilepsy in adults, characterized by high therapy resistance. Studies suggest a complete loss of astrocytic coupling in TLE, preceding dysfunctional changes in neurons, indicating that astrocyte uncoupling may be a causal event in epilepsy initiation. However, further research is needed to fully understand the role of gap junction channels in epilepsy and develop effective therapeutic strategies targeting astrocytes.