摘要
老年痴呆(AD)是一种进行性神经退行性疾病,它是美国第四大死因,也是成年发作性痴呆的最常见原因。AD的主要标志是beta淀粉样蛋白造成的老年性淀粉样斑块和主要由磷酸化tau蛋白组成的神经元纤维缠结(NFT)。虽然有许多药物被考虑用作对抗AD,但只有有限的药物被确定可能具有神经保护能力。硫黄素T曾被用作对脑内beta淀粉样斑块进行染色。该研究把硫黄素T(ThT)和载体(初始型式)用40mg/kg的剂量给转基因(B6C3 APP PS1;AD-Tg)小鼠灌服,从4个月大直到9个月大处死。与控制中的小鼠相比,用ThT处理的雌或雄转基因小鼠的淀粉样斑块数量的显著减少。此外,GFAP和Amylo-Glo标记表明星形细胞肥大在ThT处理的动物中程度最低。同样,检测出活化小胶质细胞的CD68标记以及Amylo-Glo标记显示小胶质细胞的活化在ThT处理的小鼠中明显较少。ThT处理的动物的Aβ-40和Aβ-42的血液浓度明显升高,这表明ThT能抑制脑内Aβ斑块的沉积,降解和/或清除。
关键词: AD,Amylo-Glo,星形胶质细胞,CD68,GFAP,小胶质细胞,神经保护作用,硫黄素T。
Current Alzheimer Research
Title:Oral Administration of Thioflavin T Prevents Beta Amyloid Plaque Formation in Double Transgenic AD Mice
Volume: 12 Issue: 9
Author(s): Sumit Sarkar, James Raymick, Balmiki Ray, Debomoy K. Lahiri, Merle G. Paule and Larry Schmued
Affiliation:
关键词: AD,Amylo-Glo,星形胶质细胞,CD68,GFAP,小胶质细胞,神经保护作用,硫黄素T。
摘要: Alzheimer’s disease (AD) is a progressive neurodegenerative disorder and the fourth leading cause of death in the United States and most common cause of adult-onset dementia. The major hallmarks of AD are the formation of senile amyloid plaques made of beta amyloid and neurofibrillary tangles (NFT) which are primarily composed of phosphorylated tau protein. Although numerous agents have been considered as providing protection against AD, identification of potential agents with neuroprotective ability is limited. Thioflavin T has been used in the past to stain amyloid beta plaques in brain. In this study, Thioflavin T (ThT) and vehicle (infant formula) were administered orally by gavage to transgenic (B6C3 APP PS1; AD-Tg) mice beginning at 4 months age and continuing until sacrifice at 9 months of age at 40mg/kg dose. The number of amyloid plaques was reduced dramatically by ThT treatment in both male and female transgenic mice compared to those in control mice. Additionally, GFAP and Amylo-Glo labeling suggest that astrocytic hypertrophy is minimized in ThT-treated animals. Similarly, CD68 labeling, which detects activated microglia, along with Amylo-Glo labeling, suggests that microglial activation is significantly less in ThT-treated mice. Both Aβ-40 and Aβ-42 concentrations in blood rose significantly in the ThT-treated animals suggesting that ThT may inhibit the deposition, degradation, and/or clearance of Aβ plaques in brain.
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Cite this article as:
Sumit Sarkar, James Raymick, Balmiki Ray, Debomoy K. Lahiri, Merle G. Paule and Larry Schmued , Oral Administration of Thioflavin T Prevents Beta Amyloid Plaque Formation in Double Transgenic AD Mice, Current Alzheimer Research 2015; 12 (9) . https://dx.doi.org/10.2174/156720501209151019105647
DOI https://dx.doi.org/10.2174/156720501209151019105647 |
Print ISSN 1567-2050 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5828 |
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