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  • Title: Dehydroepiandrosterone's antiepileptic action in FeCl3-induced epileptogenesis involves upregulation of glutamate transporters.
    Author: Mishra M, Singh R, Mukherjee S, Sharma D.
    Journal: Epilepsy Res; 2013 Sep; 106(1-2):83-91. PubMed ID: 23891458.
    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.
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