Department of Internal Medicine, University of Nevada Las Vegas, School of Medicine, Las Vegas, NV, USA.
Department of Anesthesiology and Pain Medicine, Korea University Ansan Hospital, Korea University College of Medicine, 123 Jeokgeum-ro, Danwon-gu, Ansan, 15355, Korea.
Neuromolecular Med. 2021 Dec;23(4):511-520. doi: 10.1007/s12017-021-08653-3. Epub 2021 Mar 26.
Previous study indicated that Ulinastatin (UTI) increased glutamine uptake by upregulation of glutamate transporters in astrocytes. These glutamate transporters have important role to improve cognitive function in hippocampus. In this study, we wanted to demonstrate whether UTI could improve learning and memory by using zebrafish behavior model and bio-markers. Zebrafish were 6-8 months of age and were 2.5-3.5 cm long. They were divided into four groups by control, 1X PBS-injected control, UTI 10,000, and 50,000 injected group. All PBS and UTI injected zebrafish were anesthetized by Tricainemethanesulphonate. We measured total time, distance moved, and frequency in each compartment of T-maze. We also measured the expression levels of glutamate transporter levels and cognitive bio-markers such as c-fos, c-jun, BDNF. UTI affected the learning and memory in zebrafish in a dose-dependent manner. In 50,000 unit/kg UTI-treated zebrafish, there were increases of time, distance, and frequency in target compartment. In 50,000 unit/kg UTI-treated zebrafish, there was an increase of time in target compartment. There was no difference among control, PBS-injected, and UTI 10,000 unit/kg-treated groups. EAAT4 glutamate transporter, c-fos and BDNF were significantly increased in 50,000 unit/kg UTI-treated group. UTI-enhanced learning and memory in zebrafish. The expressions of EAAT4 glutamate transporter, c- fos and BDNF in zebrafish were highly correlated may play a role.
先前的研究表明，尿胰蛋白酶抑制剂（UTI）通过上调星形胶质细胞中的谷氨酸转运体增加谷氨酰胺摄取。这些谷氨酸转运体对改善海马体的认知功能具有重要作用。在这项研究中，我们想用斑马鱼行为模型和生物标志物来证明 UTI 是否可以改善学习和记忆。斑马鱼年龄为 6-8 个月，体长为 2.5-3.5 厘米。它们通过对照组、1X PBS 注射对照组、10000 和 50000 UTI 注射组进行分组。所有 PBS 和 UTI 注射的斑马鱼均用三卡因甲磺酸盐麻醉。我们测量了 T 迷宫每个隔间的总时间、移动距离和频率。我们还测量了谷氨酸转运体水平和认知生物标志物（如 c-fos、c-jun、BDNF）的表达水平。UTI 以剂量依赖的方式影响斑马鱼的学习和记忆。在 50000 单位/千克 UTI 处理的斑马鱼中，目标隔间的时间、距离和频率均增加。在 50000 单位/千克 UTI 处理的斑马鱼中，目标隔间的时间增加。对照组、PBS 注射组和 10000 单位/千克 UTI 处理组之间没有差异。50000 单位/千克 UTI 处理组的 EAAT4 谷氨酸转运体、c-fos 和 BDNF 显著增加。UTI 增强了斑马鱼的学习和记忆。斑马鱼中 EAAT4 谷氨酸转运体、c-fos 和 BDNF 的表达高度相关，可能发挥作用。
