Abstract
This study investigated the effects of neuregulin-1β (NRG1β) after middle cerebral artery occlusion/reperfusion (MCAO/R) in rats to evaluate whether they occur via the cyclin-dependent kinase (Cdk)5 signaling pathway. One hundred adult male Wistar rats were randomly divided into sham, MCAO/R, treatment (NRG1β), inhibitor (roscovitine; Ros), and inhibitor + treatment (Ros + NRG1β) groups. The MCAO/R model was established using the intraluminal thread method. The neurobehavioral function was evaluated by the modified neurological severity score (mNSS). The cerebral infarction volume (CIV) was measured by triphenyl tetrazolium chloride (TTC) staining. Morphological changes were observed by hematoxylin-eosin (HE) staining. The apoptotic cell index (ACI) was detected by the terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) assay. Immunohistochemistry and Western blotting were performed to detect the expression of calpain 1, p35/p25 (regulatory binding partners of Cdk5), Cdk5, and p-Tau in neurons. The neuronal morphology in the MCAO/R, NRG1β, Ros + NRG1β, and Ros groups differed compared to the sham group; the mNSS, CIV, ACI, and the expression of calpain 1, p35/p25, Cdk5, and p-Tau were significantly increased in all four groups (P < 0.05). In the NRG1β, Ros and Ros + NRG1β groups, the neuronal morphology was significantly improved compared to the MCAO/R group, as were the mNSS, CIV, and ACI. The levels of calpain 1, p35/p25, and p-Tau were decreased compared with the MCAO/R group (P < 0.05), while the Cdk5 expression was not significantly different (P > 0.05). NRG1β may exert neuroprotective effects by inhibiting the expression of calpain 1, p35/p25, and p-Tau after cerebral ischemia-reperfusion injury.
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Funding
This work was supported by grants from the National Natural Science Foundation of China (81274116), the Taishan Scholars Construction Project Excellent Innovative Team of Shandong Province, and the Youth Fund Project of the Affiliated Hospital of Qingdao University. None of these organizations was involved in the design, performance, collection of data, analysis, interpretation, or presentation of this study.
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The National Institutes of Health Guide for the Care and Use of Laboratory Animals was used as a guide for the design of all animal-related studies. All animal-related experiments were performed using protocols approved by our institute (The Ethics Committee of Qingdao University Medical College, QUMC 2011-09).
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Zhang, R., Liu, C., Ji, Y. et al. Neuregulin-1β Plays a Neuroprotective Role by Inhibiting the Cdk5 Signaling Pathway after Cerebral Ischemia-Reperfusion Injury in Rats. J Mol Neurosci 66, 261–272 (2018). https://doi.org/10.1007/s12031-018-1166-3
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DOI: https://doi.org/10.1007/s12031-018-1166-3