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Analysis of the antiepileptic, ethosuximide impacts on neurogenesis of rat forebrain stem cells.

Abstract
Specific GABAergic interneurons in the hilus are lost in animal models with temporal-lobe epilepsy (TLE). Some preclinical evidence has indicated that GABAergic cells may provide relief from seizures in these models. This study was aimed to examine the ability of ethosuximide, an anticonvulsant drug, to promote neurogenesis in 3-day-old rat forebrain cortex stem cells. Most of the cells were found to be nestin-positive undifferentiated neural stem cells prior to their exposure to ethosuximide. It was noted that the number and percentage of tubulin β-III immunopositive neurons were increased after 6 days treatment with ethosuximide. Upon bFGF withdrawal, exposure to ethosuximide differentiated the stem cells to MAP2 positive neural cells (7.18 ± 0.43, 21.766 ± 0.55 and 41.57 ± 0.5 for control, 0.1 and 1 μM, respectively). GABA immunofluorescence images illustrated that ethosuximide increased GABAergic neurons (7.19 ± 0.32, 23.23 ± 0.55, and 46.30 ± 0.44 for control, 0.1 and 1 μM, respectively). Additionally, BrdU immunofluorescence assay showed that ethosuximide-enhanced nucleus proliferation in the neuronal stem cells. Therefore, the results of this study suggest that ethosuximide may compensate damage caused by seizure attacks and possibly other neuronal loss disorders.
AuthorsKiana Sondossi, Maryam Majdzadeh, Padideh Ghaeli, Mohammad Hossein Ghahremani, Hamed Shafaroodi, Babak Paknejad, Seyed Nasser Ostad
JournalFundamental & clinical pharmacology (Fundam Clin Pharmacol) Vol. 28 Issue 5 Pg. 512-8 (Oct 2014) ISSN: 1472-8206 [Electronic] England
PMID24354536 (Publication Type: Journal Article)
Copyright© 2013 Société Française de Pharmacologie et de Thérapeutique.
Chemical References
  • Anticonvulsants
  • Ethosuximide
Topics
  • Animals
  • Animals, Newborn
  • Anticonvulsants (pharmacology)
  • Ethosuximide (pharmacology)
  • GABAergic Neurons (drug effects)
  • Neurogenesis (drug effects)
  • Prosencephalon (cytology, drug effects)
  • Rats
  • Rats, Sprague-Dawley
  • Stem Cells (drug effects)

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