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

Jiandong Hao, Peter R. Rapp, Abba E. Leffler, Shoshana R. Leffler, William G M Janssen, Wendy Lou, Heather McKay, Jeffrey A Roberts, Susan L. Wearne, Patrick R. Hof, John Morrison

Research output: Contribution to journalArticlepeer-review

204 Scopus citations


Long-term cyclic treatment with 17β-estradiol reverses age-related impairment in ovariectomized rhesus monkeys on a test of cognitive function mediated by the prefrontal cortex (PFC). Here,weexamined 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. 17β-Estradiol did not affect several parameters such as total dendritic length and branching. In contrast, 17β-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 17β-estradiol treatment, and that increased dendritic spine density and altered spine morphology may contribute to the cognitive benefits of such treatment.

Original languageEnglish (US)
Pages (from-to)2571-2578
Number of pages8
JournalJournal of Neuroscience
Issue number9
StatePublished - Mar 1 2006
Externally publishedYes


  • Cognition
  • Estradiol
  • Hormone
  • Neocortex
  • Plasticity
  • Pyramidal cell

ASJC Scopus subject areas

  • Neuroscience(all)


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