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

YÜKSEL M., BİBEROĞLU K., ÖNDER S., AKBULUT K. G., TACAL Ö.

BIOCHIMIE, cilt.146, ss.105-112, 2018 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 146
  • Basım Tarihi: 2018
  • Doi Numarası: 10.1016/j.biochi.2017.12.004
  • Dergi Adı: BIOCHIMIE
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Sayfa Sayıları: ss.105-112
  • Anahtar Kelimeler: Alzheimer's disease, Amyloid-beta peptide, Cholinesterase inhibitor, Toluidine blue O, Tau hyperphosphorylation, 3xTg-AD mice, METHYLENE-BLUE, A-BETA, CHOLINESTERASE-INHIBITORS, ACETYLCHOLINESTERASE PROMOTES, PRECURSOR PROTEIN, TAU-AGGREGATION, COGNITION, BUTYRYLCHOLINESTERASE, NEUROTOXICITY, PEPTIDES
  • Gazi Üniversitesi Adresli: Evet

Özet

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.