Department of Chemical Pharmacology, Faculty of Pharmacy, Meijo University, 150 Yagotoyama, Tenpaku-ku, Nagoya 468-8503, Japan.
Department of Chemical Pharmacology, Faculty of Pharmacy, Meijo University, 150 Yagotoyama, Tenpaku-ku, Nagoya 468-8503, Japan.
Eur J Pharmacol. 2019 Jan 5;842:57-63. doi: 10.1016/j.ejphar.2018.10.037. Epub 2018 Oct 27.
In the pathophysiology of Alzheimer's disease (AD), the deposition of amyloid β protein (Aβ) is associated with oxidative stress, leading to cognitive impairment and neurodegeneration. Betaine (glycine betaine or trimethylglycine), known as an osmolyte and methyl donor in mammalian cells, has been reported to suppress the proinflammatory response and oxidative stress in the kidneys, but the effects of betaine on brain diseases remain to be determined. Here, to investigate the effects of betaine treatment on cognitive impairment and the increase in oxidative stress in the brain of an AD animal model, we performed a novel object recognition test and measured the malondialdehyde (MDA; a marker of oxidative stress) levels in the frontal cortex and hippocampus of mice intracerebroventricularly injected with Aβ, an active fragment of Aβ. Betaine prevented cognitive impairment as well as increases of the cortical and hippocampal MDA levels in Aβ-injected mice. Of note, NNC 05-2090, a selective inhibitor of betaine/GABA transporter-1 (GAT2/BGT-1), reduced the preventive effects of betaine on Aβ-induced cognitive impairment without affecting the increased MDA levels in the brain of Aβ-injected mice. As betaine is used as a substrate of GAT2/BGT-1, these results suggest that betaine is transported through GAT2/BGT-1 and prevents cognitive impairment in Aβ-injected mice, but GAT2/BGT-1 function is not required for the antioxidant effects of betaine.
在阿尔茨海默病（AD）的病理生理学中，淀粉样β蛋白（Aβ）的沉积与氧化应激有关，导致认知障碍和神经退行性变。甜菜碱（甘氨酸甜菜碱或三甲氨基丁酸）作为哺乳动物细胞中的渗透剂和甲基供体，已被报道可抑制肾脏的促炎反应和氧化应激，但甜菜碱对脑部疾病的影响仍有待确定。在这里，为了研究甜菜碱治疗对 AD 动物模型认知障碍和大脑氧化应激增加的影响，我们进行了新物体识别测试，并测量了经 Aβ（Aβ 的活性片段）脑室内注射的小鼠前额叶皮层和海马体中的丙二醛（MDA；氧化应激的标志物）水平。甜菜碱可预防 Aβ 注射小鼠的认知障碍以及皮质和海马 MDA 水平的升高。值得注意的是，NNC 05-2090，一种选择性的甜菜碱/ GABA 转运蛋白-1（GAT2/BGT-1）抑制剂，降低了甜菜碱对 Aβ 诱导的认知障碍的预防作用，而不影响 Aβ 注射小鼠大脑中 MDA 水平的升高。由于甜菜碱可用作 GAT2/BGT-1 的底物，这些结果表明甜菜碱通过 GAT2/BGT-1 转运并预防 Aβ 注射小鼠的认知障碍，但 GAT2/BGT-1 功能不是甜菜碱抗氧化作用所必需的。
