Astrocyte uncoupling as a cause of human temporal lobe epilepsy

Objective: Anti-epileptic drugs usually act on neurons, and can be associated with side-effects and refractoriness. Recently, the role of glia (non-electrically excitable cells in the brain) in epilepsy is being examined. One type of glia called astrocytes (star-shaped glial cells) has been shown to undergo tremendous changes in the epileptic brain; hence, examining its role in epilepsy could lead to the development of newer and better therapies for epilepsy. In a recent study, the authors studied astrocytes in tissue resected from the brain of people with epilepsy. To understand the role of astrocytes in epilepsy in greater detail, they also used a mouse model of epilepsy.

Results: One of the ways astrocytes keep excitability of neurons under check is by buffering potassium (K+) ions. Tight regulation of K+ concentration is important because an increase in K+ ions can cause seizures. Astrocytes are connected to each other and astrocytes help clearance of K+ ions by distributing K+ ions throughout the astrocytic network. The authors of this study found that astrocytes were no longer connected or coupled in tissue from a subset of patients with epilepsy. In a mouse model of epilepsy where seizures were elicited by administration of a chemoconvulsant, the authors found that uncoupling of astrocytes is a relatively early phenomenon.

Interpretation: There is a great interest in the role of astrocytes in epilepsy. The results of this study suggest that since uncoupling of astrocytes occurs in epilepsy, targeting astrocytes may be a novel therapeutic strategy.

Summary for specialists