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使用功能分子影像学评价牛磺酸对阿尔茨海默病的神经保护作用。

Evaluation of the neuroprotective effect of taurine in Alzheimer's disease using functional molecular imaging.

机构信息

Division of Applied RI, Korea Institute of Radiological and Medical Sciences, 75 Nowon-ro, Nowon-gu, Seoul, 01812, Korea.

Division of Radiation Effects, Korea Institute of Radiological and Medical Sciences, Seoul, Korea.

出版信息

Sci Rep. 2020 Sep 23;10(1):15551. doi: 10.1038/s41598-020-72755-4.

Abstract

Alzheimer's disease (AD) is a chronic neurodegenerative disorder and the leading cause of dementia, but therapeutic treatment options are limited. Taurine has been reported to have neuroprotective properties against dementia, including AD. The present study aimed to investigate the treatment effect of taurine in AD mice by functional molecular imaging. To elucidate glutamate alterations by taurine, taurine was administered to 5xFAD transgenic mice from 2 months of age, known to apear amyloid deposition. Then, we performed glutamate positron emission tomography (PET) imaging studies for three groups (wild-type, AD, and taurine-treated AD, n = 5 in each group). As a result, brain uptake in the taurine-treated AD group was 31-40% higher than that in the AD group (cortex: 40%, p < 0.05; striatum: 32%, p < 0.01; hippocampus: 36%, p < 0.01; thalamus: 31%, p > 0.05) and 3-14% lower than that in the WT group (cortex: 10%, p > 0.05; striatum: 15%, p > 0.05; hippocampus: 14%, p > 0.05; thalamus: 3%, p > 0.05). However, we did not observe differences in Aβ pathology between the taurine-treated AD and AD groups in immunohistochemistry experiments. Our results reveal that although taurine treatment did not completely recover the glutamate system, it significantly increased metabolic glutamate receptor type 5 brain uptake. Therefore, taurine has therapeutic potential against AD.

摘要

阿尔茨海默病(AD)是一种慢性神经退行性疾病,也是痴呆症的主要病因,但治疗选择有限。牛磺酸已被报道具有神经保护作用,可预防痴呆症,包括 AD。本研究旨在通过功能分子成像研究牛磺酸对 AD 小鼠的治疗作用。为了阐明牛磺酸对谷氨酸的改变,我们从 2 个月大开始向 5xFAD 转基因小鼠(已知会出现淀粉样蛋白沉积)给予牛磺酸。然后,我们对三组(野生型、AD 和牛磺酸治疗的 AD,每组 5 只)进行了谷氨酸正电子发射断层扫描(PET)成像研究。结果,牛磺酸治疗的 AD 组的脑摄取量比 AD 组高 31-40%(皮质:40%,p<0.05;纹状体:32%,p<0.01;海马体:36%,p<0.01;丘脑:31%,p>0.05),比 WT 组低 3-14%(皮质:10%,p>0.05;纹状体:15%,p>0.05;海马体:14%,p>0.05;丘脑:3%,p>0.05)。然而,在免疫组织化学实验中,我们没有观察到牛磺酸治疗的 AD 组和 AD 组之间 Aβ 病理学的差异。我们的结果表明,尽管牛磺酸治疗并没有完全恢复谷氨酸系统,但它显著增加了代谢型谷氨酸受体 5 的脑摄取。因此,牛磺酸具有治疗 AD 的潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/50ee/7511343/91b567d2024d/41598_2020_72755_Fig1_HTML.jpg

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