Activated astrocytes attenuate neocortical seizures in rodent models through driving Na⁺-K⁺-ATPase.

ABSTRACT: Epileptic seizures are widely regarded to occur as a result of the excitation-inhibition imbalance from a neuro-centric view. Although astrocyte-neuron interactions are increasingly recognized in seizure, elementary questions about the causal role of astrocytes in seizure remain unanswered. Here we show that optogenetic activation of channelrhodopsin-2-expressing astrocytes effectively attenuates neocortical seizures in rodent models. This anti-seizure effect is independent from classical calcium signaling, and instead related to astrocytic Na⁺-K⁺-ATPase-mediated buffering K⁺, which activity-dependently inhibits firing in highly active pyramidal neurons during seizure. Compared with inhibition of pyramidal neurons, astrocyte stimulation exhibits anti-seizure effects with several advantages, including a wider therapeutic window, large-space efficacy, and minimal side effects. Finally, optogenetic-driven astrocytic Na⁺-K⁺-ATPase shows promising therapeutic effects in a chronic focal cortical dysplasia epilepsy model. Together, we uncover a promising anti-seizure strategy with optogenetic control of astrocytic Na⁺-K⁺-ATPase activity, providing alternative ideas and a potential target for the treatment of intractable epilepsy.

SUBMITTER: Zhao J 

PROVIDER: S-EPMC9681834 | biostudies-literature | 2022 Nov

REPOSITORIES: biostudies-literature