Wang Jiutao, Song Lingzhen, Zhang Qi, Zhang Wei, An Lei, Zhang Yamei, Tong Dewen, Zhao Baoyu, Chen Shulin, Zhao Shanting
College of Veterinary Medicine, Northwest A&F University, Yangling, Shaanxi 712100, PR China.
College of Veterinary Medicine, Northwest A&F University, Yangling, Shaanxi 712100, PR China.
Toxicol Lett. 2015 Jan 5;232(1):263-70. doi: 10.1016/j.toxlet.2014.11.017. Epub 2014 Nov 18.
Swainsonine (SW) is an indolizidine triol plant alkaloid isolated from the species Astragalus, colloquially termed locoweed. Ingestion induces severe neurological symptoms of livestock and wildlife, including ataxia, trembling, exaggerated fright reactions. Toxicity to the central and peripheral nervous system is caused by inhibition of lysosomal a-mannosidase (AMA) and accumulation of intracellular oligosaccharide. However, the effects of SW on adult neurogenesis and cognition have remained unclear. Therefore, the present study was conducted to examine the effects of SW on adult neurogenesis and learning as well as memory performance in adult mice. SW (10μg/mL in drinking water) was administered orally to mice for 4 weeks. Our results showed that SW reduced proliferation and survival of neural progenitor cells (NPCs) in culture, and in the hippocampus of adult mice. In addition, exposure to SW led to down-regulation of doublecortin (DCX) and synaptophysin (SYP) in the hippocampus. However, caspase 3 and glial fibrillary acidic protein (GFAP) levels were significantly increased in SW-treated mice. Finally, SW-treated mice exhibited deficits in hippocampus-dependent spatial learning and memory. Our findings suggest that SW affects adult neurogenesis and cognitive function.
苦马豆素（SW）是一种从黄芪属植物中分离出的吲哚里西啶三醇类植物生物碱，俗称疯草。摄入后会导致家畜和野生动物出现严重的神经症状，包括共济失调、颤抖、过度惊吓反应。对中枢和外周神经系统的毒性是由溶酶体α-甘露糖苷酶（AMA）的抑制和细胞内寡糖的积累引起的。然而，SW对成体神经发生和认知的影响仍不清楚。因此，本研究旨在探讨SW对成年小鼠成体神经发生、学习及记忆能力的影响。将SW（饮用水中浓度为10μg/mL）口服给予小鼠4周。我们的结果表明，SW降低了培养物中以及成年小鼠海马体中神经祖细胞（NPC）的增殖和存活率。此外，接触SW导致海马体中双皮质素（DCX）和突触素（SYP）的表达下调。然而，SW处理的小鼠中半胱天冬酶3和胶质纤维酸性蛋白（GFAP）水平显著升高。最后，SW处理的小鼠在海马体依赖的空间学习和记忆方面表现出缺陷。我们的研究结果表明，SW会影响成体神经发生和认知功能。
