Research on ketamine in mediating autophagy and inhibiting apoptosis of astrocytes in cerebral cortex of rats through NF-Œ∫B pathway
Authors: X-X Bu
J Shen
X Li
T Hong
C Yang
J Yang
Journal: European review for medical and pharmacological sciences (2018)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: ketamine; autophagy; apoptosis; astrocytes; cerebral cortex
Affiliations: Department of Anesthesiology, First People's Hospital of Changzhou & Third Affiliated Hospital of Suzhou University, Changzhou, Jiangsu, China. .

Abstract:  Objective: To investigate the effects of ketamine on autophagy and apoptosis of astrocytes in the cerebral cortex of rats, and determine whether nuclear factor-Œ∫B (NF-Œ∫B) pathway is involved in the regulation of autophagy and apoptosis of astrocytes. Materials and methods: A total of 36 male Sprague-Dawley (SD) rats were randomly divided into 3 groups: control group (Group C: intraperitoneal injection of equal amount of normal saline), glutamic acid group (Group G: intraperitoneal injection of 1 mg/kg glutamic acid) and glutamic acid + ketamine group (Group GK: intraperitoneal injection of 1 mg/kg glutamic acid and then injection of 5 mg/kg ketamine after 30 min). The cerebral cortex of rats in each group was taken after successive administration for 5 d. The number of glial fibrillary acidic protein (GFAP)-positive cells in the cerebral cortex of rats in each group was detected via immunofluorescence. The number of terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL)-positive cells (apoptotic cells) in the cerebral cortex was detected via TUNEL staining. The levels of inflammatory factors were detected using the enzyme-linked immunosorbent assay (ELISA) kit. Moreover, the expressions of autophagy-related proteins and apoptosis-related proteins in the cerebral cortex were detected via Western blotting, and the expressions of IŒ∫B-a and NF-Œ∫Bp65 were also detected. Results: The results of immunofluorescence showed that the number of GFAP-positive cells in the cerebral cortex of rats in Group G was significantly increased compared with that in Group C (p&lt;0.01), and it was significantly decreased in Group GK compared with that in Group G (p&lt;0.01). The results of TUNEL staining revealed that the number of TUNEL-positive cells in the cerebral cortex in Group G was significantly larger than that in Group C, and it was significantly smaller in Group GK than that in Group G (p&lt;0.01). Results of ELISA demonstrated that compared with those in Group C, the contents of interleukin-6 (IL-6) and tumor necrosis factor-a (TNF-a) in Group G were significantly increased (p&lt;0.01), but the content of IL-10 was significantly decreased (p&lt;0.01). Compared with those in Group G, the contents of IL-6 and TNF-a in Group GK were significantly decreased (p&lt;0.01), but the level of IL-10 was statistically elevated (p&lt;0.01). Compared with those in Group C, the levels of LC3 II/I and cleaved caspase-3 in the cerebral cortex in Group G were significantly increased (p&lt;0.01), but the p62 level and B-cell lymphoma-2/Bcl-2 associated X protein (Bcl-2/Bax) ratio were significantly decreased (p&lt;0.01). In Group GK, the levels of LC3 II/I and cleaved caspase-3 were reduced, but the p62 level and Bcl-2/Bax ratio were increased. The expressions of IŒ∫B-Œ± and NF-Œ∫Bp65 in Group G were significantly decreased compared with those in Group C (p&lt;0.01), and they were significantly higher in Group GK than those in Group G (p&lt;0.01). Conclusions: Ketamine can reduce the glutamic acid-induced activation of astrocytes in the cerebral cortex, inhibit the autophagy and alleviate the apoptosis of astrocytes, the process of which is mediated by the NF-Œ∫B pathway, which provides the new molecular basis of ketamine in protecting astrocytes. 

Retracted: No

PubPeer comments:
 Fig 1  D, Flow cytometry showed cell apoptosis after LPS or and pcDNAu2010TUG1 treatments .  The marked panel previously occurred as  LPS+sh-NEAT1 in [Chen et al (2018)] ...  As  si-PVT1 in [Huang et al (2017)] ...  As  Control in [Guo Chen (2018)] .  If I had commissioned a manuscript from this papermill, I would be disappointed by the non-uniqueness of the material. , 
 Figs 2E and 4C show more of these stylised imitations of what a FACS plot should look like.  Readers will recognise tt least two of them from [Figs 3(C) and 5(C)] of Guo Chen (2018), but it seems unnecessary to labour the point. , 
 #2 Two of the panels from 2E and 4C also appear in Figs 2D and 4D of [Liu et al (2018)] .   , 
 This paper belongs to a set of over 400 papers (as per February 2020) that share very similar Western blots with tadpole-like shaped bands, the same background pattern, and striking similarities in title structures, paper layout, bar graph design, and - in a subset - flow cytometry panels. Despite these similarities, these papers are authored by researchers from different departments and institutes, with almost no overlap in authors. The list of these papers is available here: https: docs.google.com spreadsheets d 1KXqTAyl4j-jVorFPMD2XRpr76LcIKJ0CVyIvRj0exYQ edit?usp=sharing A more detailed description of this set of papers, suspected to all be generated by a common source, a paper mill , can be found here: * https: forbetterscience.com 2020 01 24 the-full-service-paper-mill-and-its-chinese-customers (January 2020) * https: scienceintegritydigest.com 2020 02 21 the-tadpole-paper-mill (February 2020) The same paper mill has been described in these papers: * Jana Christopher - Systematic fabrication of scientific images revealed - FEBS Letters (2018) - https: febs.onlinelibrary.wiley.com doi full 10.1002 1873-3468.13201 * Jennifer A Byrne and Jana Christopher - Digital magic, or the dark arts of the 21st centuryu2014how can journals and peer reviewers detect manuscripts and publications from paper mills? - FEBS Letters (2020) - https: febs.onlinelibrary.wiley.com doi full 10.1002 1873-3468.13747 , 
 Retracted [25 September 2020] . ---------------------------------------- u201cDownregulation of lncRNA TUG1 contributes to the development of sepsisu2010associated acute kidney injury via regulating miRu2010142u20103p sirtuin 1 axis and modulating NFu2010u03baB pathway,u201d by Xiaodi Liu, Chengying Hong, Shipin Wu, Shiling Song, Zhi Yang, Lin Cao, Tongwei Song, and Ying Yang, J Cell Biochem. 2019; 11331u201311341: The above article, published online on March 4, 2019 in Wiley Online Library , has been retracted by agreement between the authors, the journal s Editor in Chief, Prof. Dr. Christian Behl, and Wiley Periodicals LLC. The retraction has been agreed following an investigation based on allegations raised by a third party. The authors admit that the experimental results are flawed, and the overall conclusions of this manuscript are not reliable. , 
 miRNAs are 22-24 nucleotide in size and the combined length of FP and RP used in PCR are greater than miRNA template size. How is it possible if they are using normal reverse transcriptase kit as they written in their method. ,