Details

Autor(en) / Beteiligte

• Lopez, Juan Pablo
• Lücken, Malte D
• Brivio, Elena
• Karamihalev, Stoyo
• Kos, Aron
• De Donno, Carlo
• Benjamin, Asaf
• Yang, Huanqing
• Dick, Alec L W
• Stoffel, Rainer
• Flachskamm, Cornelia
• Ressle, Andrea
• Roeh, Simone
• Huettl, Rosa-Eva
• Parl, Andrea
• Eggert, Carola
• Novak, Bozidar
• Yan, Yu
• Yeoh, Karin
• Holzapfel, Maria
• Hauger, Barbara
• Harbich, Daniela
• Schmid, Bianca
• Di Giaimo, Rossella
• Turck, Christoph W
• Schmidt, Mathias V
• Deussing, Jan M
• Eder, Matthias
• Dine, Julien
• Theis, Fabian J
• Chen, Alon

Titel

Ketamine exerts its sustained antidepressant effects via cell-type-specific regulation of Kcnq2

Ist Teil von

• Neuron (Cambridge, Mass.), 2022-07

Ort / Verlag

United States

Erscheinungsjahr

2022

Link zum Volltext

Quelle

Free E-Journal (出版社公開部分のみ）

Beschreibungen/Notizen

• A single sub-anesthetic dose of ketamine produces a rapid and sustained antidepressant response, yet the molecular mechanisms responsible for this remain unclear. Here, we identified cell-type-specific transcriptional signatures associated with a sustained ketamine response in mice. Most interestingly, we identified the Kcnq2 gene as an important downstream regulator of ketamine action in glutamatergic neurons of the ventral hippocampus. We validated these findings through a series of complementary molecular, electrophysiological, cellular, pharmacological, behavioral, and functional experiments. We demonstrated that adjunctive treatment with retigabine, a KCNQ activator, augments ketamine's antidepressant-like effects in mice. Intriguingly, these effects are ketamine specific, as they do not modulate a response to classical antidepressants, such as escitalopram. These findings significantly advance our understanding of the mechanisms underlying the sustained antidepressant effects of ketamine, with important clinical implications.