Toluidine Blue O Modifies Hippocampal Amyloid Pathology In A Transgenic Mouse Model Of Alzheimer'S Disease
| Autor: | Kevser Biberoglu, K. Gonca Akbulut, Seda Onder, Melike Yuksel, Ozden Tacal |
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| Rok vydání: | 2018 |
| Předmět: |
Male
0301 basic medicine Genetically modified mouse medicine.medical_specialty Amyloid Tolonium chloride Hyperphosphorylation Mice Transgenic tau Proteins Hippocampal formation Hippocampus Biochemistry Mice Protein Aggregates 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Alzheimer Disease Internal medicine mental disorders medicine Amyloid precursor protein Animals Tolonium Chloride Phosphorylation Cholinesterase Amyloid beta-Peptides biology Chemistry General Medicine medicine.disease Disease Models Animal 030104 developmental biology Endocrinology biology.protein Alzheimer's disease 030217 neurology & neurosurgery |
| Popis: | 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. (C) 2017 Elsevier B.V. and Societe Francaise de Biochimie et Biologie Moleculaire (SFBBM). All rights reserved. |
| Databáze: | OpenAIRE |
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