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
International Journal of Molecular Medicine
Join Editorial Board Propose a Special Issue
Print ISSN: 1107-3756 Online ISSN: 1791-244X
Journal Cover
June-2018 Volume 41 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
June-2018 Volume 41 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

Ephrin‑b3 modulates hippocampal neurogenesis and the reelin signaling pathway in a pilocarpine‑induced model of epilepsy

  • Authors:
    • Tian‑Tian Liu
    • Yi Li
    • Yi Shu
    • Bo Xiao
    • Li Feng
  • View Affiliations / Copyright

    Affiliations: Department of Neurology, Xiangya Hospital, Central South University, Changsha, Hunan 410008, P.R. China, Department of Neurology, University of Massachusetts Medical School, Worcester, MA 01604, USA, Department of Neurology, Second Xiangya Hospital, Central South University, Changsha, Hunan 410008, P.R. China
    Copyright: © Liu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 3457-3467
    |
    Published online on: March 7, 2018
       https://doi.org/10.3892/ijmm.2018.3543
  • 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

Ephrin‑B3 is important in the regulation of cell proliferation, differentiation and migration via cell‑cell contact, and can activate the reelin pathway during brain development. However, the effect of ephrin‑B3 on hippocampal neurogenesis and the reelin pathway in epilepsy remains to be fully elucidated. In the present study, the expression of ephrin‑B3 in pilocarpine‑induced status epilepticus (SE) rats was investigated. SYBR Green‑based reverse transcription‑quantitative polymerase chain reaction analysis, immunohistochemical labeling and western blot analysis were used to detect the gene and protein expression levels of ephrin‑B3 and reelin pathway proteins. Immunofluorescence staining of doublecortin (DCX) was utilized to analyze hippocampal neurogenesis. The data revealed that the mRNA and protein expression levels of ephrin‑B3 in the hippocampus decreased during the spontaneous seizure period. Of note, the expression of reelin and its downstream phosphorylation disabled 1 (p‑Dab1) were also notably decreased during the spontaneous seizure period, which showed similar dynamic changes as in the expression of ephrin‑B3. In addition, it was found that the number of DCX‑labeled neuronal progenitor cells was increased in the hippocampus following pilocarpine‑induced SE. To further clarify the role of ephrin‑B3 in neurogenesis and the reelin pathway in epilepsy, an exogenous ephrin‑B3 clustering stimulator, EphB3‑Fc, was infused into the bilateral hippocampus of the rats post‑SE. Following EphB3‑Fc injection, it was found that the expression levels of reelin and p‑Dab1 were significantly increased in the epileptic rats following EphB3‑Fc injection. The number of DCX‑labeled neuronal progenitor cells was reduced in the hippocampus of the epileptic rats. Furthermore, the intensity and frequency of spontaneous recurrent seizures and electroencephalographic seizures were attenuated in the epileptic rats post‑injection. These results demonstrated the critical role of ephrin‑B3 in regulation of the reelin pathway and hippocampal neurogenesis in epilepsy, providing experimental evidence that ephrin‑B3 functions as a potential protective factor in epilepsy, at least in animals.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

Figure 6

View References

1 

Moshe SL, Perucca E, Ryvlin P and Tomson T: Epilepsy: New advances. Lancet. 385:884–898. 2015. View Article : Google Scholar

2 

Liu TT, Feng L, Liu HF, Shu Y and Xiao B: Altered axon initial segment in hippocampal newborn neurons, associated with recurrence of temporal lobe epilepsy in rats. Mol Med Rep. 16:3169–3178. 2017. View Article : Google Scholar : PubMed/NCBI

3 

Li Y, Peng Z, Xiao B and Houser CR: Activation of ERK by spontaneous seizures in neural progenitors of the dentate gyrus in a mouse model of epilepsy. Exp Neurol. 224:133–145. 2010. View Article : Google Scholar : PubMed/NCBI

4 

von Bohlen und Halbach O: Immunohistological markers for proliferative events, gliogenesis, and neurogenesis within the adult hippocampus. Cell Tissue Res. 345:1–19. 2011. View Article : Google Scholar : PubMed/NCBI

5 

Parent JM and Kron MM: Neurogenesis and Epilepsy. 2012.

6 

Ishii K, Kubo K, Endo T, Yoshida K, Benner S, Ito Y, Aizawa H, Aramaki M, Yamanaka A, Tanaka K, et al: Neuronal Heterotopias affect the activities of distant brain areas and lead to behavioral deficits. J Neurosci. 35:12432–12445. 2015. View Article : Google Scholar : PubMed/NCBI

7 

Klein R and Kania A: Ephrin signalling in the developing nervous system. Curr Opin Neurobiol. 27C:16–24. 2014. View Article : Google Scholar

8 

Chumley MJ, Catchpole T, Silvany RE, Kernie SG and Henkemeyer M: EphB receptors regulate stem/progenitor cell proliferation, migration, and polarity during hippocampal neurogenesis. J Neurosci. 27:13481–13490. 2007. View Article : Google Scholar : PubMed/NCBI

9 

Furne C, Ricard J, Cabrera JR, Pays L, Bethea JR, Mehlen P and Liebl DJ: EphrinB3 is an anti-apoptotic ligand that inhibits the dependence receptor functions of EphA4 receptors during adult neurogenesis. Biochim Biophys Acta. 1793:231–238. 2009. View Article : Google Scholar :

10 

Antion MD, Christie LA, Bond AM, Dalva MB and Contractor A: Ephrin-B3 regulates glutamate receptor signaling at hippocampal synapses. Mol Cell Neurosci. 45:378–388. 2010. View Article : Google Scholar : PubMed/NCBI

11 

Forster E: Reelin, neuronal polarity and process orientation of cortical neurons. Neuroscience. 269:102–111. 2014. View Article : Google Scholar : PubMed/NCBI

12 

Senturk A, Pfennig S, Weiss A, Burk K and Acker-Palmer A: Ephrin Bs are essential components of the Reelin pathway to regulate neuronal migration. Nature. 472:356–360. 2011. View Article : Google Scholar : PubMed/NCBI

13 

Leeb C, Eresheim C and Nimpf J: Clusterin is a ligand for apolipoprotein E receptor 2 (ApoER2) and very low density lipoprotein receptor (VLDLR) and signals via the Reelin-signaling pathway. J Biol Chem. 289:4161–4172. 2014. View Article : Google Scholar : PubMed/NCBI

14 

Bosch C, Masachs N, Exposito-Alonso D, Martínez A, Teixeira CM, Fernaud I, Pujadas L, Ulloa F, Comella JX, DeFelipe J, et al: Reelin regulates the maturation of dendritic spines, synaptogenesis and glial ensheathment of newborn granule cells. Cereb Cortex. 26:4282–4298. 2016. View Article : Google Scholar : PubMed/NCBI

15 

Racine RJ: Modification of seizure activity by electrical stimulation. II. Motor seizure. Electroencephalogr Clin Neurophysiol. 32:281–294. 1972. View Article : Google Scholar : PubMed/NCBI

16 

Khazipov R, Zaynutdinova D, Ogievetsky E, Valeeva G, Mitrukhina O, Manent JB and Represa A: Atlas of the postnatal rat brain in stereotaxic coordinates. Front Neuroanat. 9:1612015. View Article : Google Scholar

17 

Kanamori K: Faster flux of neurotransmitter glutamate during seizure-Evidence from 13C-enrichment of extracellular glutamate in kainate rat model. PLoS One. 12:e01748452017. View Article : Google Scholar

18 

Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2−ΔΔC T method. Methods. 25:402–408. 2001. View Article : Google Scholar

19 

Wu Q, Li Y, Shu Y, Feng L, Zhou L, Yue ZW, Luo ZH, Wu ZG and Xiao B: NDEL1 was decreased in the CA3 region but increased in the hippocampal blood vessel network during the spontaneous seizure period after pilocarpine-induced status epilepticus. Neuroscience. 268:276–283. 2014. View Article : Google Scholar : PubMed/NCBI

20 

Lisabeth EM, Falivelli G and Pasquale EB: Eph receptor signaling and ephrins. Cold Spring Harb Perspect Biol. 5:2013. View Article : Google Scholar : PubMed/NCBI

21 

Hruska M and Dalva MB: Ephrin regulation of synapse formation, function and plasticity. Mol Cell Neurosci. 50:35–44. 2012. View Article : Google Scholar : PubMed/NCBI

22 

Ricard J, Salinas J, Garcia L and Liebl DJ: EphrinB3 regulates cell proliferation and survival in adult neurogenesis. Mol Cell Neurosci. 31:713–722. 2006. View Article : Google Scholar : PubMed/NCBI

23 

Piccinin S, Cinque C, Calo L, Molinaro G, Battaglia G, Maggi L, Nicoletti F, Melchiorri D, Eusebi F, Massey PV, et al: Interaction between Ephrins and mGlu5 metabotropic glutamate receptors in the induction of long-term synaptic depression in the hippocampus. J Neurosci. 30:2835–2843. 2010. View Article : Google Scholar : PubMed/NCBI

24 

Shu Y, Xiao B, Wu Q, Liu T, Du Y, Tang H, Chen S, Feng L, Long L and Li Y: The Ephrin-A5/EphA4 interaction modulates neurogenesis and angiogenesis by the p-Akt and p-ERK pathways in a mouse model of TLE. Mol Neurobiol. 53:561–576. 2016. View Article : Google Scholar

25 

Kron MM, Zhang H and Parent JM: The developmental stage of dentate granule cells dictates their contribution to seizure-induced plasticity. J Neurosci. 30:2051–2059. 2010. View Article : Google Scholar : PubMed/NCBI

26 

Parent JM, Yu TW, Leibowitz RT, Geschwind DH, Sloviter RS and Lowenstein DH: Dentate granule cell neurogenesis is increased by seizures and contributes to aberrant network reorganization in the adult rat hippocampus. J Neurosci. 17:3727–3738. 1997.PubMed/NCBI

27 

Song C, Xu W, Zhang X, Wang S, Zhu G, Xiao T, Zhao M and Zhao C: CXCR4 antagonist AMD3100 suppresses the long-term abnormal structural changes of newborn neurons in the intraventricular kainic acid model of epilepsy. Mol Neurobiol. 53:1518–1532. 2016. View Article : Google Scholar

28 

Kobow K, Jeske I, Hildebrandt M, Hauke J, Hahnen E, Buslei R, Buchfelder M, Weigel D, Stefan H, Kasper B, et al: Increased reelin promoter methylation is associated with granule cell dispersion in human temporal lobe epilepsy. J Neuropathol Exp Neurol. 68:356–364. 2009. View Article : Google Scholar : PubMed/NCBI

29 

Haas CA and Frotscher M: Reelin deficiency causes granule cell dispersion in epilepsy. Exp Brain Res. 200:141–149. 2010. View Article : Google Scholar

30 

Michelucci R, Pulitano P, Di Bonaventura C, Binelli S, Luisi C, Pasini E, Striano S, Striano P, Coppola G, La Neve A, et al: The clinical phenotype of autosomal dominant lateral temporal lobe epilepsy related to reelin mutations. Epilepsy Behav. 68:103–107. 2017. View Article : Google Scholar : PubMed/NCBI

31 

Baek ST, Copeland B, Yun EJ, Kwon SK, Guemez-Gamboa A, Schaffer AE, Kim S, Kang HC, Song S, Mathern GW, et al: An AKT3-FOXG1-reelin network underlies defective migration in human focal malformations of cortical development. Nat Med. 21:1445–1454. 2015. View Article : Google Scholar : PubMed/NCBI

32 

Korn MJ, Mandle QJ and Parent JM: Conditional disabled-1 deletion in mice alters hippocampal neurogenesis and reduces seizure threshold. Front Neurosci. 10:632016. View Article : Google Scholar : PubMed/NCBI

33 

Dobrzanski P, Hunter K, Jones-Bolin S, Chang H, Robinson C, Pritchard S, Zhao H and Ruggeri B: Antiangiogenic and anti-tumor efficacy of EphA2 receptor antagonist. Cancer Res. 64:910–919. 2004. View Article : Google Scholar : PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Liu TT, Li Y, Shu Y, Xiao B and Feng L: Ephrin‑b3 modulates hippocampal neurogenesis and the reelin signaling pathway in a pilocarpine‑induced model of epilepsy. Int J Mol Med 41: 3457-3467, 2018.
APA
Liu, T., Li, Y., Shu, Y., Xiao, B., & Feng, L. (2018). Ephrin‑b3 modulates hippocampal neurogenesis and the reelin signaling pathway in a pilocarpine‑induced model of epilepsy. International Journal of Molecular Medicine, 41, 3457-3467. https://doi.org/10.3892/ijmm.2018.3543
MLA
Liu, T., Li, Y., Shu, Y., Xiao, B., Feng, L."Ephrin‑b3 modulates hippocampal neurogenesis and the reelin signaling pathway in a pilocarpine‑induced model of epilepsy". International Journal of Molecular Medicine 41.6 (2018): 3457-3467.
Chicago
Liu, T., Li, Y., Shu, Y., Xiao, B., Feng, L."Ephrin‑b3 modulates hippocampal neurogenesis and the reelin signaling pathway in a pilocarpine‑induced model of epilepsy". International Journal of Molecular Medicine 41, no. 6 (2018): 3457-3467. https://doi.org/10.3892/ijmm.2018.3543
Copy and paste a formatted citation
x
Spandidos Publications style
Liu TT, Li Y, Shu Y, Xiao B and Feng L: Ephrin‑b3 modulates hippocampal neurogenesis and the reelin signaling pathway in a pilocarpine‑induced model of epilepsy. Int J Mol Med 41: 3457-3467, 2018.
APA
Liu, T., Li, Y., Shu, Y., Xiao, B., & Feng, L. (2018). Ephrin‑b3 modulates hippocampal neurogenesis and the reelin signaling pathway in a pilocarpine‑induced model of epilepsy. International Journal of Molecular Medicine, 41, 3457-3467. https://doi.org/10.3892/ijmm.2018.3543
MLA
Liu, T., Li, Y., Shu, Y., Xiao, B., Feng, L."Ephrin‑b3 modulates hippocampal neurogenesis and the reelin signaling pathway in a pilocarpine‑induced model of epilepsy". International Journal of Molecular Medicine 41.6 (2018): 3457-3467.
Chicago
Liu, T., Li, Y., Shu, Y., Xiao, B., Feng, L."Ephrin‑b3 modulates hippocampal neurogenesis and the reelin signaling pathway in a pilocarpine‑induced model of epilepsy". International Journal of Molecular Medicine 41, no. 6 (2018): 3457-3467. https://doi.org/10.3892/ijmm.2018.3543
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