Reelin regulates neuronal progenitor migration in intact and epileptic hippocampus

Chao Gong, Tsu Wei Wang, Holly S. Huang, Jack M. Parent

Research output: Contribution to journalArticle

149 Citations (Scopus)

Abstract

Dentate granule cell (DGC) neurogenesis persists throughout life in the mammalian hippocampal dentate gyrus and increases after epileptogenic insults. The DGC layer in human and experimental mesial temporal lobe epilepsy (mTLE) often shows abnormal dispersion and the appearance of hilar-ectopic DGCs. In the pilocarpine mTLE model, hilar-ectopic DGCs arise as a result of an aberrant chain migration of neural progenitors. Reelin is a secreted migration guidance cue that persists in the adult rodent and human hippocampus. Wetested the hypothesis that loss of Reelin in the epileptic dentate gyrus leads to aberrant chain migration of DGC precursors. We found that interneuron subsets typically lost in human and experimental mTLE express Reelin, and DGC progenitors express the downstream Reelin signaling molecule Disabled 1 (Dab1). Prolonged seizures decreased Reelin immunoreactivity in the adult rat dentate gyrus and increased Dab1 expression in hilar-ectopic neuroblasts. Exogenous Reelin increased detachment of chain-migrating neuroblasts in dentate gyrus explants, and blockade of Reelin signaling increased chain migration. These findings suggest that Reelin modulates DGC progenitor migration to maintain normal DGC integration in the neonatal and adult mammalian dentate gyrus. Loss of Reelin expression in the epileptic adult hippocampus, moreover, likely contributes to ectopic chain migration and aberrant integration of newborn DGCs.

Original languageEnglish
Pages (from-to)1803-1811
Number of pages9
JournalJournal of Neuroscience
Volume27
Issue number8
DOIs
Publication statusPublished - 2007 Feb 21

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Keywords

  • Epileptogenesis
  • Hippocampus
  • Neural stem cell
  • Neurogenesis
  • Neuronal migration
  • Reelin

ASJC Scopus subject areas

  • Neuroscience(all)

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