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Estrogen alters spine number and morphology in prefrontal cortex of aged female rhesus monkeys.

Long-term cyclic treatment with 17beta-estradiol reverses age-related impairment in ovariectomized rhesus monkeys on a test of cognitive function mediated by the prefrontal cortex (PFC). Here, we examined potential neurobiological substrates of this effect using intracellular loading and morphometric analyses to test the possibility that the cognitive benefits of hormone treatment are associated with structural plasticity in layer III pyramidal cells in PFC area 46. 17beta-Estradiol did not affect several parameters such as total dendritic length and branching. In contrast, 17beta-estradiol administration increased apical and basal dendritic spine density, and induced a shift toward smaller spines, a response linked to increased spine motility, NMDA receptor-mediated activity, and learning. These results document that, although the aged primate PFC is vulnerable in the absence of factors such as circulating estrogens, it remains responsive to long-term cyclic 17beta-estradiol treatment, and that increased dendritic spine density and altered spine morphology may contribute to the cognitive benefits of such treatment.

Pubmed ID: 16510735


  • Hao J
  • Rapp PR
  • Leffler AE
  • Leffler SR
  • Janssen WG
  • Lou W
  • McKay H
  • Roberts JA
  • Wearne SL
  • Hof PR
  • Morrison JH


The Journal of neuroscience : the official journal of the Society for Neuroscience

Publication Data

March 1, 2006

Associated Grants

  • Agency: NIA NIH HHS, Id: AG06647
  • Agency: NIA NIH HHS, Id: AG10606
  • Agency: NIA NIH HHS, Id: AG16765
  • Agency: NIMH NIH HHS, Id: MH58911
  • Agency: NIMH NIH HHS, Id: MH60734
  • Agency: NCRR NIH HHS, Id: RR16754

Mesh Terms

  • Aging
  • Animals
  • Behavior, Animal
  • Cell Size
  • Dendritic Spines
  • Estradiol
  • Female
  • Imaging, Three-Dimensional
  • Isoquinolines
  • Macaca mulatta
  • Neurons
  • Ovariectomy
  • Prefrontal Cortex