2025-04-25 シカゴ大学
<関連情報>
- https://news.uchicago.edu/story/study-examines-how-laughing-gas-could-treat-depression
- https://www.nature.com/articles/s41467-025-57951-y
亜酸化窒素はSK2チャネル阻害を介して第5層前頭前野ニューロンを活性化し、抗うつ効果をもたらす Nitrous oxide activates layer 5 prefrontal neurons via SK2 channel inhibition for antidepressant effect
Joseph Cichon,Thomas T. Joseph,Xinguo Lu,Andrzej Z. Wasilczuk,Max B. Kelz,Steven J. Mennerick,Charles F. Zorumski &Peter Nagele
Nature Communications Published:03 April 2025
DOI:https://doi.org/10.1038/s41467-025-57951-y
Abstract
Nitrous oxide (N2O) induces rapid and durable antidepressant effects. The cellular and circuit mechanisms mediating this process are not known. Here we find that a single dose of inhaled N2O induces rapid and specific activation of layer V (L5) pyramidal neurons in the cingulate cortex of rodents exposed to chronic stress conditions. N2O-induced L5 activation rescues a stress-associated hypoactivity state, persists following exposure, and is necessary for its antidepressant-like activity. Although NMDA-receptor antagonism is believed to be a primary mechanism of action for N2O, L5 neurons activate even when NMDA-receptor function is attenuated through both pharmacological and genetic approaches. By examining different molecular and circuit targets, we identify N2O-induced inhibition of calcium-sensitive potassium (SK2) channels as a key molecular interaction responsible for driving specific L5 activity along with ensuing antidepressant-like effects. These results suggest that N2O-induced L5 activation is crucial for its fast antidepressant action and this effect involves novel and specific molecular actions in distinct cortical cell types.