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.

• Authors: Junli Zhao, Jinyi Sun, Yang Zheng, Yanrong Zheng, Yuying Shao, Yulan Li, Fan Fei, Cenglin Xu, Xiuxiu Liu, Shuang Wang, Yeping Ruan, Jinggen Liu, Shumin Duan, Zhong Chen, Yi Wang
• Journal: Nature communications (Nat Commun) Vol. 13 Issue 1 Pg. 7136 (11 21 2022) ISSN: 2041-1723 [Electronic] England
• PMID: 36414629 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2022. The Author(s).

Chemical References

• Adenosine Triphosphatases
• Ions

Topics

• Animals
• Astrocytes
• Adenosine Triphosphatases
• Rodentia
• Neocortex
• Ions