Synaptic estrogen receptor-alpha levels in prefrontal cortex in female rhesus monkeys and their correlation with cognitive performance.
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.
Wang
Athena C J
AC
Department of Neuroscience, Mount Sinai School of Medicine, New York, New York 10029, USA.
Hara
Yuko
Y
Janssen
William G M
WG
Rapp
Peter R
PR
Morrison
John H
JH
D000704:Analysis of Variance; D000818:Animals; D003071:Cognition / Q000187:drug effects / Q000502:physiology*; D004958:Estradiol / Q000378:metabolism / Q000494:pharmacology; D047628:Estrogen Receptor alpha / Q000378:metabolism*; D005260:Female; D008253:Macaca mulatta; D008570:Memory, Short-Term / Q000187:drug effects / Q000502:physiology; D016253:Microscopy, Immunoelectron; D009483:Neuropsychological Tests; D010052:Ovariectomy; D017397:Prefrontal Cortex / Q000187:drug effects / Q000378:metabolism*; D013569:Synapses / Q000187:drug effects / Q000378:metabolism*
D047628:Estrogen Receptor alpha; D004958:Estradiol