First Author | Zhao J | Year | 2022 |
Journal | Nat Commun | Volume | 13 |
Issue | 1 | Pages | 7136 |
PubMed ID | 36414629 | Mgi Jnum | J:334204 |
Mgi Id | MGI:7387644 | Doi | 10.1038/s41467-022-34662-2 |
Citation | Zhao J, et al. (2022) Activated astrocytes attenuate neocortical seizures in rodent models through driving Na(+)-K(+)-ATPase. Nat Commun 13(1):7136 |
abstractText | 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. |