BRILLIANT BLUE G IMPROVES COGNITION IN AN ANIMAL MODEL OF ALZHEIMER'S DISEASE AND INHIBITS AMYLOID-β-INDUCED LOSS OF FILOPODIA AND DENDRITE SPINES IN HIPPOCAMPAL NEURONS

BRILLIANT BLUE G IMPROVES COGNITION IN AN ANIMAL MODEL OF ALZHEIMER'S DISEASE AND INHIBITS AMYLOID-β-INDUCED LOSS OF FILOPODIA AND DENDRITE SPINES IN HIPPOCAMPAL NEURONS
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DOI:
10.1016/j.neuroscience.2014.08.036
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发表时间:
2014-10-24
期刊:
影响因子:
3.3
通讯作者:
Wang, Q.
Wang, Q.
中科院分区:
医学3区
文献类型:
--
作者:
Chen, X.;Hu, J.;Wang, Q.

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淀粉样β蛋白沉积是阿尔茨海默病(AD)的特征之一。许多研究报告称,Aβ多肽,尤其是寡聚体,会导致记忆力下降和其他认知缺陷。然而,几乎没有有效的干预措施来终止甚至延缓AD的进展。亮蓝G(BBG)是一种安全的三苯基甲烷染料和P2X7拮抗剂,已有报道对神经炎症、缺血、脊髓损伤和神经退行性疾病具有保护作用。在此,我们报道了系统地给予BBG减轻了通过向海马CA1区注射可溶性AD肽而造成的小鼠AD模型的空间记忆障碍和认知障碍。此外,我们还发现,给予BBG可以防止Aβ诱导的海马神经元丝足和棘密度的丧失。结论:补肾活血颗粒可预防由可溶性Aβ毒性所致的学习记忆障碍和认知障碍,并能促进AD模型小鼠海马神经元树突棘的发育。考虑到BBG的安全性和血脑屏障(BBB)通透性,我们的数据表明BBG作为一种新的治疗AD的方法是有潜力的。(C)2014年IBRO。爱思唯尔有限公司出版。保留所有权利。
Deposits of amyloid-beta (A beta) protein are one of the hallmarks of Alzheimer's disease (AD). Numerous studies report that the A beta peptide, especially in the oligomeric form, causes memory decline and other cognitive deficits. However, there have been very few effective interventions for termination or even delay of AD progression. Brilliant Blue G (BBG), a safe triphenylmethane dye and P2X7 antagonist, has been reported to have protective effects on neuroinflammation, ischemia, spinal injury and neurodegenerative disorders. Here we report that systematic administration of BBG diminishes spatial memory impairment and cognitive deficits in a mouse AD model produced by injecting soluble AD peptide into the hippocampal CA1 region. In addition, we show that A beta-induced loss of filopodia and spine density in cultured hippocampal neurons was prevented by administration of BBG. We conclude that BBG prevents the learning and memory impairment and cognitive deficits induced by the toxicity of soluble A beta, and improves the development of dendritic spines in hippocampal neurons in an AD model mouse. Considering the safety and blood-brain-barrier (BBB)-permeability of BBG, our data suggest a potential for BBG as a new therapy for AD. (c) 2014 IBRO. Published by Elsevier Ltd. All rights reserved.