Toluidine blue O modifies hippocampal amyloid pathology in a transgenic mouse model of Alzheimer's disease

作者：Yuksel Melike^*; Biberoglu Kevser; Onder Seda; Akbulut K Gonca; Tacal Ozden^*

来源：Biochimie, 2018, 146: 105-112.

DOI：10.1016/j.biochi.2017.12.004

• Alzheimer's disease
• Amyloid-beta peptide
• Cholinesterase inhibitor
• Toluidine blue O
• Tau hyperphosphorylation
• 3xTg-AD mice

Recently, we have 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 4mg/kg TBO or vehicle daily for 30 days. TBO treatment significantly reduced the levels of insoluble A beta 40 and A beta 42 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 beta-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.

• 出版日期2018-3