Dehydroepiandrosterone's antiepileptic action in FeCl3-induced epileptogenesis involves upregulation of glutamate transporters.

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  • Author(s): Mishra M;Mishra M; Singh R; Mukherjee S; Sharma D
  • Source:
    Epilepsy research [Epilepsy Res] 2013 Sep; Vol. 106 (1-2), pp. 83-91. Date of Electronic Publication: 2013 Jul 26.
  • Publication Type:
    Journal Article; Research Support, Non-U.S. Gov't
  • Language:
    English
  • Additional Information
    • Source:
      Publisher: Elsevier Science Publishers Country of Publication: Netherlands NLM ID: 8703089 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1872-6844 (Electronic) Linking ISSN: 09201211 NLM ISO Abbreviation: Epilepsy Res Subsets: MEDLINE
    • Publication Information:
      Original Publication: Amsterdam : Elsevier Science Publishers, c1987-
    • Subject Terms:
    • Abstract:
      Dehydroepiandrosterone (DHEA), a neuroactive androgen steroid, has antiepileptic action in iron-induced experimental epilepsy (which models post-traumatic clinical epilepsy). In iron-induced epilepsy increased extracellular glutamate resulting from its reduced glial uptake due to the down-regulation (decreased expression) of transporters (glial and or neuronal) is active during epileptogenesis. The present study was aimed at determining whether the mechanism of antiepileptic action of DHEA involved upregulation (increased expression) of glutamate transporters. Iron-induced epileptogenesis was performed in rats by FeCl3 injection into the cerebral cortex. DHEA was administered intraperitoneally to the iron-induced epileptic rats for 7, 14 and 21 days. Levels of glutamate transporters mRNAs expression were measured using quantitative PCR in the hippocampus during the chronic phase of iron-induced epileptogenesis. There were significant reductions in the glutamate transporter mRNAs in epileptogenesis. DHEA treatment resulted in a significant elevation of glutamate transporters: GLT-1, GLAST and EACC-1 mRNA indicating that the DHEA treatment induced upregulation of these transporters. The results are of significance in respect of the mechanism of the antiepileptic action of neurosteroids and the glutamate transporters as therapeutic targets in glutamatergic epileptogenesis.
      (Copyright © 2013 Elsevier B.V. All rights reserved.)
    • Contributed Indexing:
      Keywords: Antiepileptic action; Dehydroepiandrosterone; Glutamate transporters; Iron-induced epilepsy; Post-traumatic epilepsy; mRNA expression
    • Accession Number:
      0 (Amino Acid Transport System X-AG)
      0 (Anticonvulsants)
      0 (Chlorides)
      0 (Excitatory Amino Acid Transporter 1)
      0 (Excitatory Amino Acid Transporter 2)
      0 (Excitatory Amino Acid Transporter 3)
      0 (Ferric Compounds)
      0 (RNA primers)
      0 (Slc1a1 protein, rat)
      0 (Slc1a2 protein, rat)
      0 (Slc1a3 protein, rat)
      3KX376GY7L (Glutamic Acid)
      459AG36T1B (Dehydroepiandrosterone)
      63231-63-0 (RNA)
      U38V3ZVV3V (ferric chloride)
    • Publication Date:
      Date Created: 20130730 Date Completed: 20140319 Latest Revision: 20161125
    • Publication Date:
      20231215
    • Accession Number:
      10.1016/j.eplepsyres.2013.06.008
    • Accession Number:
      23891458