Synaptic estrogen receptor-α levels in prefrontal cortex in female rhesus monkeys and their correlation with cognitive performance

Athena C J Wang, Yuko Hara, William G M Janssen, Peter R. Rapp, John Morrison

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Abstract

In rat hippocampus, estrogen receptor-α(ER-α) can initiate nongenomic signaling mechanisms that modulate synaptic plasticity in response to either circulating or locally synthesized estradiol (E). Here we report quantitative electron microscopic data demonstrating that ER-α is present within excitatory synapses in dorsolateral prefrontal cortex (dlPFC) of young and aged ovariectomized female rhesus monkeys with and without E treatment. There were no treatment or age effects on the percentage of excitatory synapses containing ER-α, nor were there any group differences in distribution of ER-α within the synapse. However, the mean size of synapses containing ER-α was larger than that of unlabeled excitatory synapses. All monkeys were tested on delayed response (DR), a cognitive test of working memory that requires dlPFC. In young ovariectomized monkeys without E treatment, presynaptic ER-α correlated with DR accuracy across memory delays. In aged monkeys that received E treatment, ER-α within the postsynaptic density (30-60 nm from the synaptic membrane) positively correlated with DR performance. Thus, although the lack of group effects suggests that ER-α is primarily in synapses that are stable across age and treatment, synaptic abundance of ER-α is correlated with individual performance in two key age/treatment groups. These data have important implications for individual differences in the cognitive outcome among menopausal women and promote a focus on cortical estrogen receptors for therapeutic efficacy with respect to cognition.

Original languageEnglish (US)
Pages (from-to)12770-12776
Number of pages7
JournalJournal of Neuroscience
Volume30
Issue number38
DOIs
StatePublished - Sep 22 2010
Externally publishedYes

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ASJC Scopus subject areas

  • Neuroscience(all)
  • Medicine(all)

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