Brain Science Institute, Korea Institute of Science and Technology (KIST), Hwarangno 14-gil 5, Seongbuk-gu, Seoul, 02792, South Korea.
Biological Chemistry Program, Korea University of Science and Technology (UST), 217 Gajungro Yuseong-gu, Daegeon, 34113, South Korea.
Adv Exp Med Biol. 2017;975 Pt 1:233-241. doi: 10.1007/978-94-024-1079-2_21.
Alzheimer's disease (AD) is the most common cause of dementia leading to severe cognitive decline. During the progression of AD, amyloid-β (Aβ) monomers aggregate into neurotoxic soluble oligomeric Aβ that causes cognitive impairments. Our previous study indicates that oral supplementation of taurine at 1000 mg/kg/day significantly ameliorates hippocampal-dependent cognitive deficits in APP/PS1 transgenic AD mouse model. However, Aβ plaques and oligomeric Aβ levels are not affected after administration of taurine and the oral dosage of taurine was relatively high. Thus, in this study, we focused on direct correlation between taurine and oligomeric Aβ, causing memory deficits in a lower oral dosage of taurine, 250 mg/kg/day. We induced AD-like cognitive impairments to adult normal mice and orally administered taurine via drinking water for 10 days. We confirmed that taurine administration improved cognitive deficits in oligomeric Aβ-infusion mice in Y-maze and passive avoidance tests without activity alteration of mice. In addition, we found that taurine directly bound to oligomeric Aβ in surface plasmon resonance analyses. Our results propose that taurine can ameliorate cognitive impairment by directly binding to oligomeric Aβ in oral administration of 250 mg/kg/day for 10 days.
阿尔茨海默病（AD）是导致严重认知能力下降的最常见痴呆症病因。在 AD 的进展过程中，淀粉样蛋白-β（Aβ）单体聚集成神经毒性可溶性寡聚 Aβ，导致认知障碍。我们之前的研究表明，每天口服 1000mg/kg 的牛磺酸可显著改善 APP/PS1 转基因 AD 小鼠模型中海马依赖性认知缺陷。然而，牛磺酸给药后 Aβ 斑块和寡聚 Aβ 水平没有受到影响，而且牛磺酸的口服剂量相对较高。因此，在这项研究中，我们专注于牛磺酸与寡聚 Aβ之间的直接相关性，以及在较低的牛磺酸口服剂量（250mg/kg/天）下导致记忆缺陷。我们诱导成年正常小鼠出现 AD 样认知障碍，并通过饮用水给予牛磺酸口服 10 天。我们证实牛磺酸给药可改善寡聚 Aβ 输注小鼠在 Y 迷宫和被动回避测试中的认知缺陷，而不改变小鼠的活动。此外，我们发现牛磺酸在表面等离子体共振分析中直接与寡聚 Aβ结合。我们的研究结果表明，牛磺酸可以通过每天口服 250mg/kg 并持续 10 天直接与寡聚 Aβ结合来改善认知障碍。
