Preventive Effect of Betaine Against Cognitive Impairments in Amyloid β Peptide-Injected Mice Through Sirtuin1 in Hippocampus
Preventive Effect of Betaine Against Cognitive Impairments in Amyloid β Peptide-Injected Mice Through Sirtuin1 in Hippocampus
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DOI：
10.1007/s11064-022-03622-z
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发表时间：
2022-05-21
影响因子：
4.4
通讯作者：
Hiramatsu, Masayuki
中科院分区：
文献类型：
--
作者：
Ibi, Daisuke;Kondo, Sari;Hiramatsu, Masayuki
在阿尔茨海默病的病理生理学中，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。我们已经报道了甜菜碱(甘氨酸甜菜碱)，一种细胞内的渗透剂和甲基供体，可以防止脑室注射Aβ(25-35)的小鼠认知障碍的发展，Aβ是Aβ的一个活性片段，与海马区的氧化应激相关，但甜菜碱的分子机制仍有待确定。在这里，为了研究甜菜碱预防Aβ(25-35)注射小鼠认知障碍的关键分子，我们对Aβ(25-35)注射的小鼠进行了认知测试和qPCR分析，其中甜菜碱在注射Aβ(25-35)的前一天开始摄入，然后持续8天。注射Aβ(25-35)分别损害了Y迷宫和物体识别测试中的短期记忆和物体识别记忆。聚合酶链式反应分析显示，在注射Aβ(25-35)的小鼠的海马区，Sirtuin1(SIRT1)的表达下调，而甜菜碱的摄入阻止了记忆障碍以及海马区SIRT1表达的减少。此外，Sirtuin家族的抑制剂sirtinol阻断了甜菜碱对记忆缺陷的预防作用。另一方面，激活SIRT1的有效化合物白藜芦醇也可以预防Aβ(25-35)注射的小鼠的记忆损伤，这表明SIRT1在甜菜碱预防Aβ暴露引起的记忆障碍中起到了致病作用。
In the pathophysiology of Alzheimer's disease, the deposition of amyloid beta peptide (A beta) is associated with oxidative stress, leading to cognitive impairment and neurodegeneration. We have already reported that betaine (glycine betaine), an osmolyte and methyl donor in cells, prevents the development of cognitive impairment in mice with intracerebroventricular injection of A beta(25-35), an active fragment of A beta, associated with oxidative stress in the hippocampus, but molecular mechanisms of betaine remain to be determined. Here, to investigate a key molecule underlying the preventive effect of betaine against cognitive impairments in A beta(25-35)-injected mice, cognitive tests and qPCR assays were performed in A beta(25-35)-injected mice with continuous betaine intake, in which intake was started a day before A beta(25-35) injection, and then continued for 8 days. The A beta(25-35) injection impaired short-term and object recognition memories in the Y-maze and object recognition tests, respectively. PCR assays revealed the down-regulation of Sirtuin1 (SIRT1), a NAD(+)-dependent deacetylase that mediates metabolic responses, in the hippocampus of A beta(25-35)-injected mice, whereas betaine intake prevented memory deficits as well as the decrease of hippocampal SIRT1 expression in A beta(25-35)-injected mice. Further, sirtinol, an inhibitor of the Sirtuin family, blocked the preventive effect of betaine against memory deficits. On the other hand, resveratrol, the potent compound that activates SIRT1, also prevented memory impairments in A beta(25-35)-injected mice, suggesting that SIRT1 plays a causative role in the preventive effect of betaine against memory deficits caused by A beta exposure.