Estrogen and aging affect the synaptic distribution of estrogen receptor beta-immunoreactivity in the CA1 region of female rat hippocampus

Estradiol (E) mediates increased synaptogenesis in the hippocampal CA1 stratum radiatum (sr) and enhances memory in young and some aged female rats, depending on dose and age. Young female rats express more estrogen receptor alpha (ER alpha) immunolabeling in CA1sr spine synapse complexes than aged rats and ERa regulation is E sensitive in young but not aged rats. The current study examined whether estrogen receptor beta (ER beta) expression in spine synapse complexes may be altered by age or E treatment. Young (3-4 months) and aged (2223 months) female rats were ovariectomized 7 days prior to implantation of silastic capsules containing either vehicle (cholesterol) or E (10% in cholesterol) for 2 days. ER beta immunoreactivity (ir) in CA1sr was quantitatively analyzed using post-embedding electron microscopy. ER beta-ir was more prominent post-synaptically than pre-synaptically and both age and E treatment affected its synaptic distribution. While age decreased the spine synaptic complex localization of ER beta-ir (i.e., within 60 nm of the pre- and postsynaptic membranes), E treatment increased synaptic ER beta in both young and aged rats. In addition, the E treatment, but not age, increased dendritic shaft labeling. This data demonstrates that like ER alpha the levels of ER beta-ir decrease in CA1 axospinous synapses with age, however, unlike ER alpha the levels of ER beta-ir increase in these synapses in both young and aged rats in response to E. This suggests that synaptic ER beta may be a more responsive target to E, particularly in aged females. (C) 2010 Elsevier B.V. All rights reserved.