Estradiol enhances neurogenesis in the dentate gyri of adult male meadow voles by increasing the survival of young granule neurons

Neuroscience. 2004;128(3):645-54. doi: 10.1016/j.neuroscience.2004.06.039.


This study investigated whether estradiol influenced the survival of new granule neurons, independent of altering cell proliferation, in the adult rodent dentate gyrus and whether estradiol-induced changes in new neuron number relate to any observed changes in hippocampus-dependent behavior. To test whether estradiol specifically promotes the survival of new neurons we injected castrated adult male meadow voles with the cell synthesis marker bromodeoxyuridine (BrdU; 50 mg/kg) twice on day 0 and then injected either estradiol (10 microg) or vehicle for 5 consecutive days either over days 1-5, days 6-10 or days 11-15 and perfused them on day 16. Estradiol doubled the number of hippocampal BrdU-labeled neurons but only when administered during a discrete period (days 6-10; P< or =0.01) when most new neurons extend their axons [J Comp Neurol 413 (1999) 146]. To test whether the estradiol-induced increase in new neuron number was related to hippocampus-dependent behavior, males were injected with BrdU twice on day 0 and with estradiol or vehicle over days 6-10 before standard Morris water maze training commenced on day 16, 5 days after the final hormone injection. As in the first study, estradiol-treated males had more BrdU-labeled cells than vehicle-treated males. On a probe trial, estradiol-treated males spent significantly more time in the training quadrant than vehicle-treated males despite similar performance between groups during acquisition and reversal training trials. Thus estradiol enhanced the survival of young neurons but only when administered during their 'axon extension' phase and this effect was related to better spatial memory in male voles.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Arvicolinae / anatomy & histology
  • Arvicolinae / physiology*
  • Bromodeoxyuridine
  • Cell Differentiation / drug effects
  • Cell Differentiation / physiology
  • Cell Division / drug effects
  • Cell Division / physiology
  • Cell Survival / drug effects
  • Cell Survival / physiology
  • Dentate Gyrus / cytology
  • Dentate Gyrus / drug effects
  • Dentate Gyrus / physiology*
  • Estradiol / pharmacology*
  • Male
  • Maze Learning / drug effects
  • Maze Learning / physiology
  • Memory / drug effects
  • Memory / physiology
  • Neurons / cytology
  • Neurons / drug effects
  • Neurons / physiology*
  • Orchiectomy
  • Sex Factors
  • Space Perception / drug effects
  • Space Perception / physiology
  • Up-Regulation / drug effects
  • Up-Regulation / physiology


  • Estradiol
  • Bromodeoxyuridine