Department of Neurobiology, Southern Medical University, Guangzhou, China.
Int J Neuropsychopharmacol. 2010 Jun;13(5):623-33. doi: 10.1017/S1461145709990733. Epub 2009 Oct 2.
Current antidepressants are clinically effective only after several weeks of administration. We show that Fuzi polysaccharide-1 (FPS), a new water-soluble polysaccharide isolated from Fuzi, which has been used to treat mood disorders in traditional Chinese medicine for centuries, increases the number of newborn cells in the dentate gyrus in adult mice, and most of these cells subsequently differentiate into new neurons. We also found that FPS administration reduces immobility in the forced swim test, and latency in the novelty suppressed-feeding test. Moreover, a 14-d regimen with FPS reverses avoidance behaviour and inhibition of hippocampal neurogenesis induced by chronic defeat stress. In contrast, imipramine, a well known antidepressant, reverses this avoidance behaviour only after 4 wk of continuous administration. Finally, acute treatment with FPS had no effect on brain monoamine levels in frontal cortex but significantly increases BDNF in the hippocampus, while the antidepressant effect and enhancement of cell proliferation induced by FPS administration were totally blocked by K252a, an inhibitor of trkB in a chronic social defeat depression model, suggesting that the neurogenic and antidepressant effects of FPS may involve BDNF signalling. In conclusion, our findings suggest that FPS could be developed as a putative antidepressant with a rapid onset of action.
目前的抗抑郁药在给药数周后才具有临床疗效。我们发现,从附子中分离得到的一种新的水溶性多糖附子多糖-1(FPS),在中医中已被用于治疗情绪障碍数百年,可增加成年小鼠齿状回中的新生细胞数量,其中大多数细胞随后分化为新的神经元。我们还发现,FPS 给药可减少强迫游泳试验中的不动性和新异环境抑制摄食试验中的潜伏期。此外,14 天的 FPS 治疗方案可逆转慢性挫败应激引起的回避行为和海马神经发生抑制。相比之下,一种著名的抗抑郁药丙咪嗪,仅在连续给药 4 周后才会逆转这种回避行为。最后,FPS 的急性治疗对前额叶皮质中的单胺类物质水平没有影响,但可显著增加海马中的 BDNF,而在慢性社交挫败抑郁模型中,trkB 抑制剂 K252a 完全阻断了 FPS 给药引起的抗抑郁作用和细胞增殖增强,这表明 FPS 的神经发生和抗抑郁作用可能涉及 BDNF 信号通路。总之,我们的研究结果表明,FPS 可作为一种具有快速作用的新型抗抑郁药进行开发。