title: Dehydroepiandrosterone's antiepileptic action in FeCl3-induced epileptogenesis involves upregulation of glutamate transporters.
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.
authors.affiliation: Neurobiology Laboratory, School of Life Sciences, Jawaharlal Nehru University, New Delhi 110067, India.
authors.forename: Monika
authors.initials: M
authors.lastname: Mishra
authors.forename: Rameshwar
authors.initials: R
authors.lastname: Singh
authors.forename: Somnath
authors.initials: S
authors.lastname: Mukherjee
authors.forename: Deepak
authors.initials: D
authors.lastname: Sharma
mesh_terms: D027322:Amino Acid Transport System X-AG / Q000378:metabolism*; D000818:Animals; D000927:Anticonvulsants; D002712:Chlorides; D003687:Dehydroepiandrosterone / Q000494:pharmacology*; D004569:Electroencephalography; D055724:Electrophysiological Phenomena / Q000502:physiology; D004827:Epilepsy / Q000139:chemically induced* / Q000517:prevention & control*; D027341:Excitatory Amino Acid Transporter 1 / Q000378:metabolism; D027342:Excitatory Amino Acid Transporter 2 / Q000378:metabolism; D050580:Excitatory Amino Acid Transporter 3 / Q000378:metabolism; D005290:Ferric Compounds; D018698:Glutamic Acid / Q000378:metabolism; D008297:Male; D016133:Polymerase Chain Reaction; D012313:RNA / Q000096:biosynthesis / Q000302:isolation & purification; D051381:Rats; D017208:Rats, Wistar; D012640:Seizures / Q000139:chemically induced / Q000517:prevention & control
chemical_list: D027322:Amino Acid Transport System X-AG; D000927:Anticonvulsants; D002712:Chlorides; D027341:Excitatory Amino Acid Transporter 1; D027342:Excitatory Amino Acid Transporter 2; D050580:Excitatory Amino Acid Transporter 3; D005290:Ferric Compounds; C034477:RNA primers; C493398:Slc1a1 protein, rat; C493395:Slc1a2 protein, rat; C493392:Slc1a3 protein, rat; D018698:Glutamic Acid; D003687:Dehydroepiandrosterone; D012313:RNA; C024555:ferric chloride
keywords: Antiepileptic action; Dehydroepiandrosterone; Glutamate transporters; Iron-induced epilepsy; Post-traumatic epilepsy; mRNA expression