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Toluidine blue O modifies hippocampal amyloid pathology in a transgenic mouse model of Alzheimer’s disease
Biochimie ( IF 3.3 ) Pub Date : 2017-12-14
Melike Yuksel, Kevser Biberoglu, Seda Onder, K. Gonca Akbulut, Ozden Tacal

Recently, we demonstrated that toluidine blue O (TBO), a phenothiazine dye, shows inhibitory effects on both cholinesterases and amyloid pathology in Alzheimer’s disease (AD) cellular model. In the present study, we aimed to determine the effects of TBO (in a purity of 85%) on amyloid and tau pathologies in a triple transgenic mouse model of AD (3xTg-AD). Beginning at 7.5 (mild pathology) or 13 (severe pathology) months of age, 3xTg-AD mice were treated intraperitoneally with 4 mg/kg TBO or vehicle daily for 30 days. TBO treatment significantly reduced the levels of insoluble Aβ40 and Aβ42 in the hippocampi of mild and severe pathology groups compared to vehicle-treated counterparts. When the levels of full-length amyloid precursor protein (APP) and β-site APP-cleaving enzyme 1 (BACE1) were assessed in 3xTg-AD mice at late pathological stage, no significant changes were observed after TBO treatment. Similarly, TBO did not recover hyperphosphorylation of tau at residues Thr181 and Ser202/Thr205 significantly in soluble and insoluble hippocampal fractions of 3xTg-AD mice. Taken together, the current study is the first in vivo report, to our knowledge, demonstrating that TBO mitigates amyloid pathology in 3xTg-AD mice with no apparent change on tau phosphorylation. Overall, the preliminary data presented here support the possible use of TBO as a disease-modifying drug for AD treatment.



中文翻译:

甲苯胺蓝O改变阿尔茨海默氏病转基因小鼠模型的海马淀粉样蛋白病理

最近,我们证明了甲苯噻吩蓝O(TBO),一种吩噻嗪染料,在阿尔茨海默氏病(AD)细胞模型中对胆碱酯酶和淀粉样蛋白病理都有抑制作用。在本研究中,我们旨在确定TBO(纯度为85%)对AD的三重转基因小鼠模型(3xTg-AD)中淀粉样蛋白和tau病理的影响。从7.5(轻度病理)或13(重度病理)月龄开始,每天对3xTg-AD小鼠腹膜内给予4 mg / kg TBO或溶媒治疗30天。与媒介物治疗的对应物相比,TBO治疗显着降低了轻度和重度病理组海马中不溶性Aβ40和Aβ42的水平。在病理晚期,评估3xTg-AD小鼠的全长淀粉样前体蛋白(APP)和β位APP裂解酶1(BACE1)的水平,TBO治疗后未观察到明显变化。同样,在3xTg-AD小鼠的可溶和不可溶海马部分,TBO不能在残基Thr181和Ser202 / Thr205上恢复tau的过度磷酸化。综上所述,目前的研究是第一个我们所知,体内报道证明TBO减轻了3xTg-AD小鼠的淀粉样蛋白病理,tau磷酸化没有明显变化。总体而言,此处提供的初步数据支持将TBO用作AD治疗的疾病缓解药物。

更新日期:2017-12-14
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