笑気ガスによるうつ病治療の可能性(Study examines how laughing gas could treat depression)

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.