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Front. Mol. Neurosci. | doi: 10.3389/fnmol.2017.00393

Indirubin derivative 7-Bromoindirubin-3-oxime (7Bio) attenuates Aβ oligomer-induced cognitive impairments in mice

 Wei Cui1*, Liping Chen1, Chunhui Huang1, Jieyi Shentu1, Minjun Wang1, Sicheng Yan1, Fei Zhou1,  Zaijun Zhang2,  Chuang Wang1, Yifan Han3 and Qinwen Wang1
  • 1Ningbo University, China
  • 2Jinan University, China
  • 3Hong Kong Polytechnic University, Hong Kong

Indirubins are natural occurring alkaloids extracted from indigo dye-containing plants. Indirubins could inhibit various kinases, and might be used to treat chronic myelocytic leukemia, cancer and neurodegenerative disorders. 7-bromoindirubin-3-oxime (7Bio), an indirubin derivative derived from indirubin-3-oxime, possesses inhibitory effects against cyclin-dependent kinase-5 (CDK5) and glycogen synthase kinase-3β (GSK3β), two pharmacological targets of Alzheimer’s disease (AD). In this study, we have discovered that 2.3-23.3 μg/kg/kg 7Bio effectively prevented β-amyloid (Aβ) oligomer-induced impairments of spatial cognition and recognition without affecting bodyweight and motor functions in mice. Moreover, 7Bio potently inhibited Aβ oligomer-induced expression of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α). Furthermore, 7Bio significantly prevented the decreased expression of synapsin-1 and PSD-95, biomarkers of pre-synaptic and post-synaptic proteins in Aβ oligomer-treated mice. The mean optical density (OD) with hyper-phosphorylated tau (pTau), glial fibrillary acidic protein (GFAP)and CD45 positive staining in the hippocampus of 7Bio-treated mice were significantly decreased compared to those of Aβ oligomer-treated mice. In addition, Western blotting analysis showed that 7Bio attenuated Aβ oligomer-decreased expression of pSer9-GSK3β. Those results suggested that 7Bio could potently inhibit Aβ oligomer-induced neuroinflammation, synaptic impairments, tau hyper-phosphorylation, and activation of astrocytes and microglia, which may contribute to the neuroprotective effects of 7Bio. Based on these findings, we expected that 7Bio might be developed as a novel anti-AD lead compound.

Keywords: Alzheimer's disease, 7-bromoindirubin-3-oxime, β-Amyloid, CDK5, GSK3β

Received: 07 Aug 2017; Accepted: 10 Nov 2017.

Edited by:

Oliver Wirths, Universitätsmedizin Göttingen, Germany

Reviewed by:

Ravi Manjithaya, Jawaharlal Nehru Centre for Advanced Scientific Research, India
Davide Tampellini, Institut National de la Santé et de la Recherche Médicale, France  

Copyright: © 2017 Cui, Chen, Huang, Shentu, Wang, Yan, Zhou, Zhang, Wang, Han and Wang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Dr. Wei Cui, Ningbo University, Ningbo, China, chester0151005@163.com