Food deprivation can rescue obesity and overweight-induced mood disorders, and promote mood performance in normal subjects. Animal studies and clinical research have revealed the antidepressant-like effect of calorie restriction, but little is known about the mechanism of calorie restriction-induced mood modification. Previous studies have found that astrocytes modulate depressive-like behaviors. Inositol 1,4,5-trisphosphate receptor type 2 (IP3R2) is the predominant isoform in mediating astrocyte Ca²⁺ signals and its genetic knockout mice are widely used to study astrocyte function in vivo. In this study, we showed that deletion of IP3R2 blocked the antidepressant-like effect induced by calorie restriction. In vivo microdialysis experiments demonstrated that calorie restriction induced an increase in ATP level in the medial prefrontal cortex (mPFC) in naïve mice but this effect disappeared in IP3R2-knockout mice, suggesting a role of astrocytic ATP in the calorie restriction-induced antidepressant effect. Further experiments showed that systemic administration and local infusion of ATP into the mPFC induced an antidepressant effect, whereas decreasing ATP by Apyrase in the mPFC blocked calorie restriction-induced antidepressant regulation. Together, these findings support a role for astrocytic ATP in the antidepressant–like effect caused by calorie restriction.

剥夺食物可以挽救肥胖和超重引起的情绪障碍，并促进正常受试者的情绪表现。动物研究和临床研究已经揭示了热量限制的抗抑郁样作用，但人们对热量限制引起的情绪改变的机制知之甚少。先前的研究发现星形胶质细胞调节抑郁样行为。 2 型肌醇 1,4,5-三磷酸受体 (IP3R2) 是介导星形胶质细胞 Ca ²⁺信号的主要亚型，其基因敲除小鼠广泛用于研究星形胶质细胞体内功能。在这项研究中，我们发现 IP3R2 的缺失可以阻断热量限制诱导的抗抑郁样作用。体内微透析实验表明，热量限制会导致初始小鼠内侧前额皮质 (mPFC) ATP 水平增加，但这种效应在 IP3R2 敲除小鼠中消失，表明星形胶质细胞 ATP 在热量限制诱导的抗抑郁作用中发挥作用。进一步的实验表明，全身给药和将 ATP 局部输注到 mPFC 中可诱导抗抑郁作用，而通过 Apyrase 减少 mPFC 中的 ATP 则可阻断热量限制诱导的抗抑郁调节。总之，这些发现支持星形细胞 ATP 在由热量限制引起的抗抑郁样作用中发挥作用。