Estradiol facilitates the release of neuropeptide y to suppress hippocampus-dependent seizures

Veronica A. Ledoux, Tereza Smejkalova, Renee M. May, Bradley M. Cooke, Catherine S. Woolley

Research output: Contribution to journalArticlepeer-review

63 Scopus citations


About one-third of women with epilepsy have a catamenial seizure pattern, in which seizures fluctuate with the menstrual cycle. Catamenial seizures occur more frequently when the ratio of circulating estradiol to progesterone is high, suggesting that estradiol is proconvulsant. We used adult female rats to test how estradiol-induced suppression of GABAergic inhibition in the hippocampus affects behavioral seizures induced by kainic acid. As expected, estradiol decreased the latency to initiate seizures, indicating increased seizure susceptibility. At the same time, however, estradiol also shortened the duration of late-stage seizures, indicating decreased seizure severity. Additional analyses showed that the decrease in seizure severity was attributable to greater release of the anticonvulsant neuropeptide, neuropeptide Y (NPY). First, blocking hippocampal NPY during seizures eliminated the estradiol-induced decrease in seizure duration. Second, light and electron microscopic studies indicated that estradiol increases the potentially releasable pool of NPY in inhibitory presynaptic boutons and facilitates the release of NPY from inhibitory boutons during seizures. Finally, the presence of estrogen receptor-α on large dense-core vesicles (LDCVs) in the hippocampus suggests that estradiol could facilitate neuropeptide release by acting directly on LDCVs themselves. Understanding how estradiol regulates NPY-containing LDCVs could point to molecular targets for novel anticonvulsant therapies.

Original languageEnglish (US)
Pages (from-to)1457-1468
Number of pages12
JournalJournal of Neuroscience
Issue number5
StatePublished - Feb 4 2009


  • CA1
  • Catamenial epilepsy
  • Electron microscopy
  • GABA
  • Kainic acid
  • Large dense-core vesicle

ASJC Scopus subject areas

  • General Neuroscience


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