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Front. Aging Neurosci. | doi: 10.3389/fnagi.2018.00303

Bilateral Implantation of Shear Stress Modifier in ApoE Knockout Mouse Induces Cognitive Impairment and Tau Abnormalities

 Shuke Nie1,  Yang Tan2,  Zhentao Zhang1,  Guiqin Chen1, Jing Xiong1, Dan Hu1, Keqiang Ye3, Yunjian Zhang2,  Xuebing Cao2, Liam Chen4* and Zhaohui Zhang1*
  • 1Department of Neurology, Renmin Hospital, Wuhan University, China
  • 2Department of Neurology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, China
  • 3Department of Pathology and Laboratory Medicine, Emory University School of Medicine, United States
  • 4Department of Pathology, School of Medicine, Johns Hopkins University, United States

Vascular cognitive impairment encompasses all causes of cerebrovascular disease that lead to cognitive decline, or overt dementia, atherosclerotic disease being the most common contributor. However, few rodent models that mimic the pathology of vascular cognitive impairment replicated the clinical cerebrovascular atherosclerosis. Here we aimed to investigate the mechanism underlying vascular cognitive impairment in an ApoE knockout mouse model fed with western style food with implantation of bilateral shear stress modifiers. We established a cognitive decline in spatial learning and memory developed in the bilateral modifier treated mice. Brain imaging and pathological examinations demonstrated reduced glucose intake and neuronal loss in hippocampus. Although no amyloid plaques or neurofibrillary tangles were observed, tau pathology including hyperphosphorylation, paired helical filament formation and pathologic truncation were found at considerable higher extent in the bilateral modifier group 8 weeks post the procedure. In addition, gliosis and microglia activation were confirmed in corpus callosum and ventral striatum. Thus, this ApoE knockout mouse model faithfully replicates the stenosis of common carotid artery and cognitive impairment following atherosclerotic deposition and global cerebral hypoperfusion. The close correlation of cognitive decline and tau pathology indicates the toxic tau species could be at least partially responsible for the neurodegenerative changes induced by the chronic hypoxia/ischemia.

Keywords: vascular cognitive impairment, shear stress modifier, Atherosclerosis, tau, GSK3β, asparagine endopeptidase, beta-amyloid, white matter injury

Received: 23 May 2018; Accepted: 13 Sep 2018.

Edited by:

Ralf J. Braun, University of Bayreuth, Germany

Reviewed by:

Mateusz G. Adamski, Jagiellonian Centre for Experimental Therapeutics (JCET), Jagiellonian University, Poland
Xiao Zhou, Nanfang Hospital, Southern Medical University, China
Yorito Hattori, Weill Cornell Medicine, Cornell University, United States
Xiuli Yang, School of Medicine, University of Maryland, United States  

Copyright: © 2018 Nie, Tan, Zhang, Chen, Xiong, Hu, Ye, Zhang, Cao, Chen and Zhang. 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) and the copyright owner(s) 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:
Prof. Liam Chen, School of Medicine, Johns Hopkins University, Department of Pathology, Baltimore, United States, Lchen99@jhmi.edu
Dr. Zhaohui Zhang, Renmin Hospital, Wuhan University, Department of Neurology, Wuhan, China, zhzhqing1990@163.com