Nature：罗敏敏团队发现抑郁症治疗新机制，带来更安全更有效的抗抑郁疗法

Core Viewpoint - The study highlights that adenosine signaling drives the antidepressant effects of ketamine and electroconvulsive therapy (ECT), presenting a potential target for developing scalable non-invasive antidepressant therapies [4]. Group 1: Mechanism of Action - Ketamine and ECT rapidly alleviate symptoms of treatment-resistant depression, but their mechanisms remain unclear, which is crucial for improving treatment precision [5]. - The research team identified adenosine signaling as the core pathway through which these interventions exert their antidepressant effects using mouse models [5]. Group 2: Key Findings - Experiments with genetically encoded adenosine sensors and real-time optical recordings showed that both therapies induce a significant surge in adenosine levels in key emotional regulation brain regions, including the medial prefrontal cortex (mPFC) and hippocampus [6]. - Disruption of A1 and A2A adenosine receptors genetically or pharmacologically eliminates the antidepressant effects of ketamine and ECT, establishing the critical role of adenosine signaling in these effects [6]. Group 3: Implications for Treatment - Adenosine signaling specifically in the mPFC drives the antidepressant effects, with ketamine enhancing adenosine levels through metabolic regulation without causing excessive neuronal activity [8]. - The research team developed ketamine derivatives that enhance adenosine signaling and demonstrate better antidepressant effects with fewer side effects at therapeutic doses [8]. - Acute intermittent hypoxia, a non-drug intervention that lowers oxygen levels, can also increase brain adenosine levels and produce antidepressant effects, similar to ketamine and ECT [8].