Department of Chemical Pharmacology, Faculty of Pharmacy, Meijo University, Tenpaku-ku, Nagoya, Japan.
J Alzheimers Dis. 2021;79(2):639-652. doi: 10.3233/JAD-200972.
The deposition of amyloid-β (Aβ) and hyperphosphorylation of tau are well-known as the pathophysiological features of Alzheimer's disease (AD), leading to oxidative stress and synaptic deficits followed by cognitive symptoms. We already demonstrated that betaine (glycine betaine) prevented cognitive impairment and hippocampal oxidative stress in mice intracerebroventricularly injected with an active fragment of Aβ, whereas the effect of betaine in chronic models of AD remains unknown.
Our objective was to investigate the effects of chronic betaine intake on cognitive impairment and aberrant expression of genes involved in synapse and antioxidant activity in the hippocampus of a genetic AD model.
We performed cognitive tests and RT-PCR in the hippocampus in 3xTg mice, a genetic AD model.
Cognitive impairment in the Y-maze and novel object recognition tests became evident in 3xTg mice at 9 months old, and not earlier, indicating that cognitive impairment in 3xTg mice developed age-dependently. To examine the preventive effect of betaine on such cognitive impairment, 3xTg mice were fed betaine-containing water for 3 months from 6 to 9 months old, and subsequently subjected to behavioral tests, in which betaine intake prevented the development of cognitive impairment in 3xTg mice. Additionally, the expression levels of genes involved in synapse and antioxidant activity were downregulated in hippocampus of 3xTg mice at 9 months old compared with age-matched wild-type mice, which were suppressed by betaine intake.
Betaine may be applicable as an agent preventing the progression of AD by improving the synaptic structure/function and/or antioxidant activity.
淀粉样蛋白-β（Aβ）沉积和 tau 过度磷酸化是阿尔茨海默病（AD）的已知病理生理学特征，导致氧化应激和突触缺陷，随后出现认知症状。我们已经证明，甜菜碱（甘氨酸甜菜碱）可预防经脑室注射 Aβ活性片段的小鼠认知障碍和海马氧化应激，而甜菜碱在 AD 慢性模型中的作用尚不清楚。
我们的目的是研究慢性甜菜碱摄入对遗传 AD 模型中海马中与突触和抗氧化活性相关的基因异常表达及认知障碍的影响。
我们在 3xTg 小鼠（一种遗传 AD 模型）的海马中进行了认知测试和 RT-PCR。
3xTg 小鼠在 9 个月大时在 Y 迷宫和新物体识别测试中出现明显的认知障碍，且不会更早，这表明 3xTg 小鼠的认知障碍呈年龄依赖性发展。为了研究甜菜碱对这种认知障碍的预防作用，3xTg 小鼠从 6 个月到 9 个月龄时饮用含甜菜碱的水，然后进行行为测试，结果显示甜菜碱摄入可预防 3xTg 小鼠认知障碍的发生。此外，与年龄匹配的野生型小鼠相比，3xTg 小鼠在 9 个月时海马中与突触和抗氧化活性相关的基因表达水平下调，而甜菜碱摄入可抑制这种下调。
甜菜碱可通过改善突触结构/功能和/或抗氧化活性，作为预防 AD 进展的药物。
