Back to Journals » Neuropsychiatric Disease and Treatment » Volume 11

Minocycline upregulates cyclic AMP response element binding protein and brain-derived neurotrophic factor in the hippocampus of cerebral ischemia rats and improves behavioral deficits

Authors Zhao Y, Xiao M, He W, Cai Z, Tang Z, Tian F

Received 5 September 2014

Accepted for publication 8 October 2014

Published 26 February 2015 Volume 2015:11 Pages 507—516


Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 3

Editor who approved publication: Dr Roger Pinder

Yu Zhao,1 Ming Xiao,2 Wenbo He,3 Zhiyou Cai3

1Department of Neurology, the Fourth Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang Province, People’s Republic of China; 2Department of Anatomy, Nanjing Medical University, Nanjing, Jiangsu, People’s Republic of China; 3Department of Neurology, Renmin Hospital, Hubei University of Medicine, Shiyan Renmin Hospital, Shiyan, Hubei Province, People’s Republic of China

Background and purpose: The cAMP response element binding protein (CREB) plays an important role in the mechanism of cognitive impairment and is also pivotal in the switch from short-term to long-term memory. Brain-derived neurotrophic factor (BDNF) seems a promising avenue in the treatment of cerebral ischemia injury since this neurotrophin could stimulate structural plasticity and repair cognitive impairment. Several findings have displayed that the dysregulation of the CREB–BDNF cascade has been involved in cognitive impairment. The aim of this study was to investigate the effect of cerebral ischemia on learning and memory as well as on the levels of CREB, phosphorylated CREB (pCREB), and BDNF, and to determine the effect of minocycline on CREB, pCREB, BDNF, and behavioral functional recovery after cerebral ischemia.
Methods: The animal model was established by permanent bilateral occlusion of both common carotid arteries. Behavior was evaluated 5 days before decapitation with Morris water maze and open-field task. Four days after permanent bilateral occlusion of both common carotid arteries, minocycline was administered by douche via the stomach for 4 weeks. CREB and pCREB were examined by Western blotting, reverse transcription polymerase chain reaction, and immunohistochemistry. BDNF was measured by immunohistochemistry and Western blotting.
Results: The model rats after minocycline treatment swam shorter distances than control rats before finding the platform (P=0.0007). The number of times the platform position was crossed for sham-operation rats was more than that of the model groups in the corresponding platform location (P=0.0021). The number of times the platform position was crossed for minocycline treatment animals was significantly increased compared to the model groups in the corresponding platform position (P=0.0016). CREB, pCREB, and BDNF were downregulated after permanent bilateral occlusion of both common carotid arteries in the model group. Minocycline increased the expression of CREB, pCREB, and BDNF, and improved cognitive suffered from impairment of permanent bilateral occlusion of both common carotid arteries.
Conclusion: Minocycline improved cognitive impairment from cerebral ischemia via enhancing CREB, pCREB, and BDNF activity in the hippocampus.

Keywords: vascular cognitive impairment, cAMP response element binding protein, cerebral ischamia, neuroprotection

Creative Commons License This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at and incorporate the Creative Commons Attribution - Non Commercial (unported, v3.0) License. By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms.

Download Article [PDF]  View Full Text [HTML][Machine readable]