Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Oncology Letters
      • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Biomedical Reports
      • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • Information for Authors
    • Information for Reviewers
    • Information for Librarians
    • Information for Advertisers
    • Conferences
  • Language Editing
Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • For Authors
    • For Reviewers
    • For Librarians
    • For Advertisers
    • Conferences
  • Language Editing
Login Register Submit
  • This site uses cookies
  • You can change your cookie settings at any time by following the instructions in our Cookie Policy. To find out more, you may read our Privacy Policy.

    I agree
Search articles by DOI, keyword, author or affiliation
Search
Advanced Search
presentation
Molecular Medicine Reports
Join Editorial Board Propose a Special Issue
Print ISSN: 1791-2997 Online ISSN: 1791-3004
Journal Cover
December-2018 Volume 18 Issue 6

Full Size Image

Sign up for eToc alerts
Recommend to Library

Journals

International Journal of Molecular Medicine

International Journal of Molecular Medicine

International Journal of Molecular Medicine is an international journal devoted to molecular mechanisms of human disease.

International Journal of Oncology

International Journal of Oncology

International Journal of Oncology is an international journal devoted to oncology research and cancer treatment.

Molecular Medicine Reports

Molecular Medicine Reports

Covers molecular medicine topics such as pharmacology, pathology, genetics, neuroscience, infectious diseases, molecular cardiology, and molecular surgery.

Oncology Reports

Oncology Reports

Oncology Reports is an international journal devoted to fundamental and applied research in Oncology.

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine is an international journal devoted to laboratory and clinical medicine.

Oncology Letters

Oncology Letters

Oncology Letters is an international journal devoted to Experimental and Clinical Oncology.

Biomedical Reports

Biomedical Reports

Explores a wide range of biological and medical fields, including pharmacology, genetics, microbiology, neuroscience, and molecular cardiology.

Molecular and Clinical Oncology

Molecular and Clinical Oncology

International journal addressing all aspects of oncology research, from tumorigenesis and oncogenes to chemotherapy and metastasis.

World Academy of Sciences Journal

World Academy of Sciences Journal

Multidisciplinary open-access journal spanning biochemistry, genetics, neuroscience, environmental health, and synthetic biology.

International Journal of Functional Nutrition

International Journal of Functional Nutrition

Open-access journal combining biochemistry, pharmacology, immunology, and genetics to advance health through functional nutrition.

International Journal of Epigenetics

International Journal of Epigenetics

Publishes open-access research on using epigenetics to advance understanding and treatment of human disease.

Medicine International

Medicine International

An International Open Access Journal Devoted to General Medicine.

Journal Cover
December-2018 Volume 18 Issue 6

Full Size Image

Sign up for eToc alerts
Recommend to Library

  • Article
  • Citations
    • Cite This Article
    • Download Citation
    • Create Citation Alert
    • Remove Citation Alert
    • Cited By
  • Similar Articles
    • Related Articles (in Spandidos Publications)
    • Similar Articles (Google Scholar)
    • Similar Articles (PubMed)
  • Download PDF
  • Download XML
  • View XML
Article Open Access

Ketamine destabilizes growth of dendritic spines in developing hippocampal neurons in vitro via a Rho‑dependent mechanism

  • Authors:
    • Sufang Jiang
    • Zimiao Hao
    • Xuze Li
    • Lijun Bo
    • Rui Zhang
    • Ying Wang
    • Xiaofeng Duan
    • Rongtian Kang
    • Lining Huang
  • View Affiliations / Copyright

    Affiliations: Department of Anesthesiology, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei 050000, P.R. China
    Copyright: © Jiang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 5037-5043
    |
    Published online on: October 2, 2018
       https://doi.org/10.3892/mmr.2018.9531
  • Expand metrics +
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )
Cited By (CrossRef): 0 citations Loading Articles...

This article is mentioned in:



Abstract

The safety of anesthetics on the developing brain has caused concern. Ketamine, an N‑methyl‑D‑aspartate receptor antagonist, is widely used as a general pediatric anesthetic. Recent studies suggested that ketamine alters the plasticity of dendritic spines in the developing brain and may be an important contributing factor to learning and cognitive impairment. However, the underlying molecular mechanism remains poorly understood. Therefore, the aim of the present study was to investigate the effect of ketamine on the plasticity of dendritic spines in cultured hippocampal neurons and the potential underlying mechanisms. After 5 days in vitro, rat hippocampal neurons were exposed to different concentrations (100, 300 and 500 µM) of ketamine for 6 h. Ketamine decreased the number and length of dendritic spines in a dose‑dependent manner. Ketamine at a concentration of 300 µM caused an upregulation of transforming protein RhoA (RhoA) and Rho‑associated kinase (ROCK) protein. These effects were inhibited by the ROCK inhibitor Y27632. These results suggested that ketamine induces loss and shortening of dendritic spines in hippocampal neurons via activation of the RhoA/ROCK signaling pathway.
View Figures

Figure 1

Figure 2

Figure 3

View References

1 

Young C, Jevtovic-Todorovic V, Qin YQ, Tenkova T, Wang H, Labruyere J and Olney JW: Potential of ketamine and midazolam, individually or in combination, to induce apoptotic neurodegeneration in the infant mouse brain. Br J Pharmacol. 146:189–197. 2005. View Article : Google Scholar : PubMed/NCBI

2 

Lee BH, Chan JT, Hazarika O, Vutskits L and Sall JW: Early exposure to volatile anesthetics impairs long-term associative learning and recognition memory. PLoS One. 9:e1053402014. View Article : Google Scholar : PubMed/NCBI

3 

DiMaggio C, Sun LS and Li G: Early childhood exposure to anesthesia and risk of developmental and behavioral disorders in a sibling birth cohort. Anesth Analg. 113:1143–1151. 2011. View Article : Google Scholar : PubMed/NCBI

4 

Green SM, Roback MG, Kennedy RM and Krauss B: Clinical practice guideline for emergency department ketamine dissociative sedation: 2011 update. Ann Emerg Med. 57:449–461. 2011. View Article : Google Scholar : PubMed/NCBI

5 

Mistry RB and Nahata MC: Ketamine for conscious sedation in pediatric emergency care. Pharmacotherapy. 25:1104–1111. 2005. View Article : Google Scholar : PubMed/NCBI

6 

Paule MG, Li M, Allen RR, Liu F, Zou X, Hotchkiss C, Hanig JP, Patterson TA, Slikker W Jr and Wang C: Ketamine anesthesia during the first week of life can cause long-lasting cognitive deficits in rhesus monkeys. Neurotoxicol Teratol. 33:220–230. 2011. View Article : Google Scholar : PubMed/NCBI

7 

Scallet AC, Schmued LC, Slikker W Jr, Grunberg N, Faustino PJ, Davis H, Lester D, Pine PS, Sistare F and Hanig JP: Developmental neurotoxicity of ketamine: Morphometric confirmation, exposure parameters, and multiple fluorescent labeling of apoptotic neurons. Toxicol Sci. 81:364–370. 2004. View Article : Google Scholar : PubMed/NCBI

8 

Matus A: Actin-based plasticity in dendritic spines. Science. 290:754–758. 2000. View Article : Google Scholar : PubMed/NCBI

9 

Rochefort NL and Konnerth A: Dendritic spines: From structure to in vivo function. EMBO Rep. 13:699–708. 2012. View Article : Google Scholar : PubMed/NCBI

10 

Blanpied TA and Ehlers MD: Microanatomy of dendritic spines: Emerging principles of synaptic pathology in psychiatric and neurological disease. Biol Psychiatry. 55:1121–1127. 2004. View Article : Google Scholar : PubMed/NCBI

11 

McCann RF and Ross DA: A Fragile balance: Dendritic Spines, Learning, and Memory. Biol Psychiatry. 82:e11–e13. 2017. View Article : Google Scholar : PubMed/NCBI

12 

Tan H, Ren RR, Xiong ZQ and Wang YW: Effects of ketamine and midazolam on morphology of dendritic spines in hippocampal CA1 region of neonatal mice. Chin Med J (Engl). 122:455–459. 2009.PubMed/NCBI

13 

Huang L and Yang G: Repeated exposure to ketamine-xylazine during early development impairs motor learning-dependent dendritic spine plasticity in adulthood. Anesthesiology. 122:821–831. 2015. View Article : Google Scholar : PubMed/NCBI

14 

Olson MF: Contraction reaction: Mechanical regulation of Rho GTPase. Trends Cell Biol. 14:111–114. 2004. View Article : Google Scholar : PubMed/NCBI

15 

Hedrick NG and Yasuda R: Regulation of Rho GTPase proteins during spine structural plasticity for the control of local dendritic plasticity. Curr Opin Neurobiol. 45:193–201. 2017. View Article : Google Scholar : PubMed/NCBI

16 

Lemkuil BP, Head BP, Pearn ML, Patel HH, Drummond JC and Patel PM: Isoflurane neurotoxicity is mediated by p75NTR-RhoA activation and actin depolymerization. Anesthesiology. 114:49–57. 2011. View Article : Google Scholar : PubMed/NCBI

17 

Zimering JH, Dong Y, Fang F, Huang L, Zhang Y and Xie Z: Anesthetic sevoflurane causes Rho-dependent filopodial shortening in mouse neurons. PLoS One. 11:e01596372016. View Article : Google Scholar : PubMed/NCBI

18 

Nagy D, Kocsis K, Fuzik J, Marosi M, Kis Z, Teichberg VI, Toldi J and Farkas T: Kainate postconditioning restores LTP in ischemic hippocampal CA1: Onset-dependent second pathophysiological stress. Neuropharmacology. 61:1026–1032. 2011. View Article : Google Scholar : PubMed/NCBI

19 

Caceres A, Banker G, Steward O, Binder L and Payne M: MAP2 is localized to the dendrites of hippocampal neurons which develop in culture. Brain Res. 315:314–318. 1984. View Article : Google Scholar : PubMed/NCBI

20 

Castaneda P, Munoz M, Garcia-Rojo G, Ulloa JL, Bravo JA, Márquez R, García-Pérez MA, Arancibia D, Araneda K, Rojas PS, et al: Association of N-cadherin levels and downstream effectors of Rho GTPases with dendritic spine loss induced by chronic stress in rat hippocampal neurons. J Neurosci Res. 93:1476–1491. 2015. View Article : Google Scholar : PubMed/NCBI

21 

Swanger SA, Mattheyses AL, Gentry EG and Herskowitz JH: ROCK1 and ROCK2 inhibition alters dendritic spine morphology in hippocampal neurons. Cell Logist. 5:e11332662016. View Article : Google Scholar : PubMed/NCBI

22 

Cohen ML, Chan SL, Way WL and Trevor AJ: Distribution in the brain and metabolism of ketamine in the rat after intravenous administration. Anesthesiology. 39:370–376. 1973. View Article : Google Scholar : PubMed/NCBI

23 

Giardina SF, Cheung NS, Reid MT and Beart PM: Kainate-induced apoptosis in cultured murine cerebellar granule cells elevates expression of the cell cycle gene cyclin D1. J Neurochem. 71:1325–1328. 1998. View Article : Google Scholar : PubMed/NCBI

24 

Soriano SG, Liu Q, Li J, Liu JR, Han XH, Kanter JL, Bajic D and Ibla JC: Ketamine activates cell cycle signaling and apoptosis in the neonatal rat brain. Anesthesiology. 112:1155–1163. 2010. View Article : Google Scholar : PubMed/NCBI

25 

Zheng X, Zhou J and Xia Y: The role of TNF-α in regulating ketamine-induced hippocampal neurotoxicity. Arch Med Sci. 11:1296–1302. 2015. View Article : Google Scholar : PubMed/NCBI

26 

De Roo M, Klauser P, Briner A, Nikonenko I, Mendez P, Dayer A, Kiss JZ, Muller D and Vutskits L: Anesthetics rapidly promote synaptogenesis during a critical period of brain development. PLoS One. 4:e70432009. View Article : Google Scholar : PubMed/NCBI

27 

Elia LP, Yamamoto M, Zang K and Reichardt LF: p120 catenin regulates dendritic spine and synapse development through Rho-family GTPases and cadherins. Neuron. 51:43–56. 2006. View Article : Google Scholar : PubMed/NCBI

28 

Newell-Litwa KA, Badoual M, Asmussen H, Patel H, Whitmore L and Horwitz AR: ROCK1 and 2 differentially regulate actomyosin organization to drive cell and synaptic polarity. J Cell Biol. 210:225–242. 2015. View Article : Google Scholar : PubMed/NCBI

29 

Pozueta J, Lefort R, Ribe EM, Troy CM, Arancio O and Shelanski M: Caspase-2 is required for dendritic spine and behavioural alterations in J20 APP transgenic mice. Nat Commun. 4:19392013. View Article : Google Scholar : PubMed/NCBI

30 

Tashiro A and Yuste R: Regulation of dendritic spine motility and stability by Rac1 and Rho kinase: Evidence for two forms of spine motility. Mol Cell Neurosci. 26:429–440. 2004. View Article : Google Scholar : PubMed/NCBI

31 

Platholi J, Herold KF, Hemmings HC Jr and Halpain S: Isoflurane reversibly destabilizes hippocampal dendritic spines by an actin-dependent mechanism. PLoS One. 9:e1029782014. View Article : Google Scholar : PubMed/NCBI

32 

Darenfed H, Dayanandan B, Zhang T, Hsieh SH, Fournier AE and Mandato CA: Molecular characterization of the effects of Y-27632. Cell Motil Cytoskeleton. 64:97–109. 2007. View Article : Google Scholar : PubMed/NCBI

33 

Kang MG, Guo Y and Huganir RL: AMPA receptor and GEF-H1/Lfc complex regulates dendritic spine development through RhoA signaling cascade. Proc Natl Acad Sci USA. 106:3549–3554. 2009. View Article : Google Scholar : PubMed/NCBI

34 

Huang L, Liu Y, Jin W, Ji X and Dong Z: Ketamine potentiates hippocampal neurodegeneration and persistent learning and memory impairment through the PKCgamma-ERK signaling pathway in the developing brain. Brain Res. 1476:164–171. 2012. View Article : Google Scholar : PubMed/NCBI

35 

Xu H, Zhang J, Zhou W, Feng Y, Teng S and Song X: The role of miR-124 in modulating hippocampal neurotoxicity induced by ketamine anesthesia. Int J Neurosci. 125:213–220. 2015. View Article : Google Scholar : PubMed/NCBI

36 

Huang L, Liu Y, Zhang P, Kang R, Liu Y, Li X, Bo L and Dong Z: In vitro dose-dependent inhibition of the intracellular spontaneous calcium oscillations in developing hippocampal neurons by ketamine. PLoS One. 8:e598042013. View Article : Google Scholar : PubMed/NCBI

37 

Liu JR, Baek C, Han XH, Shoureshi P and Soriano SG: Role of glycogen synthase kinase-3β in ketamine-induced developmental neuroapoptosis in rats. Br J Anaesth. 110 Suppl 1:i3–i9. 2013. View Article : Google Scholar : PubMed/NCBI

38 

Yang G, Chang PC, Bekker A, Blanck TJ and Gan WB: Transient effects of anesthetics on dendritic spines and filopodia in the living mouse cortex. Anesthesiology. 115:718–726. 2011. View Article : Google Scholar : PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Jiang S, Hao Z, Li X, Bo L, Zhang R, Wang Y, Duan X, Kang R and Huang L: Ketamine destabilizes growth of dendritic spines in developing hippocampal neurons in vitro via a Rho‑dependent mechanism. Mol Med Rep 18: 5037-5043, 2018.
APA
Jiang, S., Hao, Z., Li, X., Bo, L., Zhang, R., Wang, Y. ... Huang, L. (2018). Ketamine destabilizes growth of dendritic spines in developing hippocampal neurons in vitro via a Rho‑dependent mechanism. Molecular Medicine Reports, 18, 5037-5043. https://doi.org/10.3892/mmr.2018.9531
MLA
Jiang, S., Hao, Z., Li, X., Bo, L., Zhang, R., Wang, Y., Duan, X., Kang, R., Huang, L."Ketamine destabilizes growth of dendritic spines in developing hippocampal neurons in vitro via a Rho‑dependent mechanism". Molecular Medicine Reports 18.6 (2018): 5037-5043.
Chicago
Jiang, S., Hao, Z., Li, X., Bo, L., Zhang, R., Wang, Y., Duan, X., Kang, R., Huang, L."Ketamine destabilizes growth of dendritic spines in developing hippocampal neurons in vitro via a Rho‑dependent mechanism". Molecular Medicine Reports 18, no. 6 (2018): 5037-5043. https://doi.org/10.3892/mmr.2018.9531
Copy and paste a formatted citation
x
Spandidos Publications style
Jiang S, Hao Z, Li X, Bo L, Zhang R, Wang Y, Duan X, Kang R and Huang L: Ketamine destabilizes growth of dendritic spines in developing hippocampal neurons in vitro via a Rho‑dependent mechanism. Mol Med Rep 18: 5037-5043, 2018.
APA
Jiang, S., Hao, Z., Li, X., Bo, L., Zhang, R., Wang, Y. ... Huang, L. (2018). Ketamine destabilizes growth of dendritic spines in developing hippocampal neurons in vitro via a Rho‑dependent mechanism. Molecular Medicine Reports, 18, 5037-5043. https://doi.org/10.3892/mmr.2018.9531
MLA
Jiang, S., Hao, Z., Li, X., Bo, L., Zhang, R., Wang, Y., Duan, X., Kang, R., Huang, L."Ketamine destabilizes growth of dendritic spines in developing hippocampal neurons in vitro via a Rho‑dependent mechanism". Molecular Medicine Reports 18.6 (2018): 5037-5043.
Chicago
Jiang, S., Hao, Z., Li, X., Bo, L., Zhang, R., Wang, Y., Duan, X., Kang, R., Huang, L."Ketamine destabilizes growth of dendritic spines in developing hippocampal neurons in vitro via a Rho‑dependent mechanism". Molecular Medicine Reports 18, no. 6 (2018): 5037-5043. https://doi.org/10.3892/mmr.2018.9531
Follow us
  • Twitter
  • LinkedIn
  • Facebook
About
  • Spandidos Publications
  • Careers
  • Cookie Policy
  • Privacy Policy
How can we help?
  • Help
  • Live Chat
  • Contact
  • Email to our Support Team