Department of Pharmacology, School of Pharmacy, Nantong University.
Invasive Technology Department, Affiliated Hospital 2 of Nantong University, First People's Hospital of Nantong City, Nantong, China.
Behav Pharmacol. 2023 Sep 1;34(6):318-329. doi: 10.1097/FBP.0000000000000738. Epub 2023 Aug 2.
Recent studies had reported that compounds that stimulate microglia could be developed as potential drugs for the treatment of depression due to their reversal effect on depression-like behaviors in chronically stressed mice. Zymosan A is a cell wall preparation of Saccharomyces cerevisiae composed of β-glucans. Based on its immuno-stimulatory activities, we hypothesized that zymosan A might have a therapeutic effect on depression. Our results showed that a single injection of zymosan A 5 h before behavioral tests at a dose of 1 or 2 mg/kg, but not at a dose of 0.5 mg/kg, reversed chronic unpredictable stress (CUS)-induced depression-like behaviors in mice in the tail suspension test, forced swimming test, and sucrose preference test. Time-dependent analysis showed that the antidepressant effect of zymosan A (2 mg/kg) in CUS mice became statistically significant at 5 and 8 h, but not at 3 h, and persisted for at least 7 days. Fourteen days after a single injection of zymosan A, no antidepressant effect was observed anymore. However, the disappeared antidepressant effect of zymosan A was restored by a second zymosan A injection (2 mg/kg, 5 h) 14 days after the first zymosan A injection. Stimulation of microglia was essential for the antidepressant effect of zymosan A because pre-inhibition of microglia by minocycline or pre-depletion of microglia by PLX3397 prevented the antidepressant effect of zymosan A. Based on these effects of zymosan A, zymosan A administration could be developed as a new strategy for the treatment of depression.
最近的研究报告称，由于能够逆转慢性应激小鼠的抑郁样行为，刺激小胶质细胞的化合物可能被开发为治疗抑郁症的潜在药物。酵母聚糖 A 是一种由 β-葡聚糖组成的酿酒酵母细胞壁制剂。基于其免疫刺激活性，我们假设酵母聚糖 A 可能对抑郁症有治疗作用。我们的结果表明，在行为测试前 5 小时单次注射 1 或 2mg/kg 剂量的酵母聚糖 A，但不是 0.5mg/kg 剂量，可逆转慢性不可预测应激（CUS）诱导的小鼠悬尾试验、强迫游泳试验和蔗糖偏好试验中的抑郁样行为。时间依赖性分析表明，酵母聚糖 A（2mg/kg）在 CUS 小鼠中的抗抑郁作用在 5 和 8 小时时具有统计学意义，但在 3 小时时没有，并且至少持续 7 天。单次注射酵母聚糖 A 14 天后，不再观察到抗抑郁作用。然而，在第一次注射酵母聚糖 A 14 天后再次注射酵母聚糖 A（2mg/kg，5 小时）恢复了其消失的抗抑郁作用。小胶质细胞的刺激对于酵母聚糖 A 的抗抑郁作用是必不可少的，因为米诺环素预先抑制小胶质细胞或 PLX3397 预先耗尽小胶质细胞可预防酵母聚糖 A 的抗抑郁作用。基于酵母聚糖 A 的这些作用，酵母聚糖 A 的给药可以开发为治疗抑郁症的新策略。
