Viral vector-mediated delivery of estrogen receptor-alpha to the hippocampus improves spatial learning in estrogen receptor-alpha knockout mice

Mol Ther. 2008 Sep;16(9):1587-93. doi: 10.1038/mt.2008.140. Epub 2008 Jul 1.


Estrogen, which influences both classical genomic and rapid membrane-associated signaling cascades, has been implicated in the regulation of hippocampal function, including spatial learning. Gene mutation studies suggest that estrogen effects are mediated by estrogen receptor-alpha (ER-alpha); however, because gonadal steroids influence the organization of the hippocampus during development, it has been difficult to distinguish developmental effects from those specific to adults. In this study we show that lentiviral delivery of the gene encoding ER-alpha to the hippocampus of adult ER-alpha-knockout (ER-alphaKO) mice restores hippocampal responsiveness to estrogen and rescues spatial learning. We propose that constitutive estrogen receptor activity is important for maintaining hippocampus-dependent memory function in adults.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Benzoates / pharmacology
  • Brain / physiology
  • COS Cells
  • Cells, Cultured
  • Chlorocebus aethiops
  • Electrophysiology
  • Estradiol / pharmacology
  • Estrogen Receptor alpha / genetics*
  • Female
  • Gene Transfer Techniques*
  • Genetic Vectors*
  • Green Fluorescent Proteins / genetics
  • Hippocampus / metabolism*
  • Immunoenzyme Techniques
  • Maze Learning*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Response Elements / physiology
  • Rhabdomyosarcoma / metabolism
  • Rhabdomyosarcoma / therapy
  • Space Perception*
  • Synaptic Transmission / physiology


  • Benzoates
  • Estrogen Receptor alpha
  • enhanced green fluorescent protein
  • Green Fluorescent Proteins
  • Estradiol