J Appl Biomed 17:99-106, 2019 | DOI: 10.32725/jab.2019.007

14-3-3ζ protein protects against brain ischemia/reperfusion injury and induces BDNF transcription after MCAO in rat

Naeemeh Khalesi1, Mojgan Bandehpour2, Mohammad Reza Bigdeli3,4, Hassan Niknejad5, Ali Dabbagh6, Bahram Kazemi1,2,*
1 Shahid Beheshti University of Medical Sciences, School of Advanced Technologies in Medicine, Biotechnology Department, Tehran, Iran
2 Shahid Beheshti University of Medical Sciences, Cellular and Molecular Biology Research Center, Tehran, Iran
3 Shahid Beheshti University, Faculty of Life Sciences and Biotechnology, Department of Animal Sciences and Biotechnology, Tehran, Iran
4 Shahid Beheshti University, Institute for Cognitive and Brain Science, Tehran, Iran
5 Shahid Beheshti University of Medical Sciences, School of Medicine, Department of Pharmacology, Tehran, Iran
6 Shahid Beheshti University of Medical Sciences, Anesthesiology Research Center, Tehran, Iran

Brain ischemia is a leading cause of death and disability worldwide that occurs when blood supply of the brain is disrupted. Brain-derived neurotrophic factor (BDNF) is a protective factor in neurodegenerative conditions. Nevertheless, there are some problems when exogenous BDNF is to be used in the clinic. 14-3-3ζ is a pro-survival highly-expressed protein in the brain that protects neurons against death. This study evaluates 14-3-3ζ effects on BDNF transcription at early time point after ischemia and its possible protective effects against ischemia damage. Human 14-3-3ζ protein was purified after expression. Rats were assigned into four groups, including sham, ischemia, and two treatment groups. Stereotaxic cannula implantation was carried out in the right cerebral ventricle. After one week, rats underwent middle cerebral artery occlusion (MCAO) surgery and received 14-3-3ζ (produced in our laboratory or standard form as control) in the middle of ischemia time. At 6 h of reperfusion after ischemia, brain parts containing the hippocampus, the cortex, the piriform cortex-amygdala and the striatum were collected for real time PCR analysis. At 24 h of reperfusion after ischemia, neurological function evaluation and infarction volume measurement were performed. The present study showed that 14-3-3ζ could up-regulate BDNF mRNA at early time point after ischemia in the hippocampus, in the cortex and in the piriform cortex-amygdala and could also improve neurological outcome and reduce infarct volume. It seems that 14-3-3ζ could be a candidate factor for increasing endogenous BDNF in the brain and a potential therapeutic factor against brain ischemia.

Keywords: 14-3-3ζ; BDNF; Brain ischemia; MCAO; Purification
Grants and funding:

This article was extracted from Naeemeh Khalesi’s PhD thesis and was supported by the School of Advanced Technologies in Medicine, Shahid Beheshti University of Medical Sciences (Grant Number: 8402), and was carried out at the Cellular and Molecular Biology Research Center, the directors of which we gratefully

Conflicts of interest:

The authors have no conflict of interests to declare.

Received: November 6, 2018; Accepted: April 15, 2019; Prepublished online: April 15, 2019; Published: June 28, 2019  Show citation

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Khalesi N, Bandehpour M, Bigdeli MR, Niknejad H, Dabbagh A, Kazemi B. 14-3-3ζ protein protects against brain ischemia/reperfusion injury and induces BDNF transcription after MCAO in rat. J Appl Biomed. 2019;17(2):99-106. doi: 10.32725/jab.2019.007. PubMed PMID: 34907731.
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