Estrogen and aging affect the synaptic distribution of estrogen receptor β-immunoreactivity in the CA1 region of female rat hippocampus - PubMed (original) (raw)

Comparative Study

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

Elizabeth M Waters et al. Brain Res. 2011.

Abstract

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 α (ERα) immunolabeling in CA1sr spine synapse complexes than aged rats and ERα regulation is E sensitive in young but not aged rats. The current study examined whether estrogen receptor β (ERβ) expression in spine synapse complexes may be altered by age or E treatment. Young (3-4 months) and aged (22-23 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. ERβ immunoreactivity (ir) in CA1sr was quantitatively analyzed using post-embedding electron microscopy. ERβ-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 ERβ-ir (i.e., within 60 nm of the pre- and post-synaptic membranes), E treatment increased synaptic ERβ in both young and aged rats. In addition, the E treatment, but not age, increased dendritic shaft labeling. This data demonstrates that like ERα the levels of ERβ-ir decrease in CA1 axospinous synapses with age, however, unlike ERα the levels of ERβ-ir increase in these synapses in both young and aged rats in response to E. This suggests that synaptic ERβ may be a more responsive target to E, particularly in aged females.

Copyright © 2010 Elsevier B.V. All rights reserved.

PubMed Disclaimer

Figures

Fig. 1

Fig. 1

Representative electron micrographs show the distribution of ERβ immunogold particles (black puncta) in the CA1 stratum radiatum of young OVX + Veh (A), young OVX + E (B), aged OVX + Veh (C) and aged OVX + E (D) rats. t, terminal; sp, dendritic spine. Bar, 100 nm

Fig. 2

Fig. 2

The overall percentage of ERβ immunoreactive axospinous synapses labeled dendritic spines is not affected by age but is significantly increased following E-replacement in both young and aged OVX rats. N = number of animals. * p < 0.02

Fig. 3

Fig. 3

Schematic drawing showing a pre- and postsynaptic profile with the eight Bin divisions used in the EM analysis.

Fig. 4

Fig. 4

Both age and estrogen altered the subcellular distribution of ERβ immunogold particles in pre- and postsynaptic profiles in the CA1sr region. A. In young OVX rats, E administration significantly increased ERβ-ir presynaptically (Bin 6) and postsynaptically (Bin 1) and in the synaptic cleft (Bin 5). B. In aged OVX rats, E administration significantly increased ERβ-ir only in Bins 1 and 8. Moreover, E administration to aged OVX significantly decreased ERβ-ir in Bin 4. * p < 0.05

Fig. 5

Fig. 5

The overall numbers of ERβ immunogold particles in dendrites are not significantly different in aged rats compared to young rats. A. Clusters of ERβ immunogold particles are visible in dendrites in the CA1sr. B. ERβ immunogold particles are significantly increased following E-replacement in both young and aged rats. * p < 0.02

Fig. 6

Fig. 6

The average distance between ERβ immunogold particles in postsynaptic profiles (dendritic spines, Bins 1 – 4) significantly increased following E administration in both young and aged rats. * p < 0.02

Fig. 7

Fig. 7

Schematic diagram depicting the effects of E administration on the levels and subcellular distribution of ERβ immunogold particles in spine synapse complexes in young and aged rats. ERβ-ir was detected in pre- and postsynaptic compartments of asymmetric synapses in the CA1sr in young and aged females. Although synapses contained fewer ERβ immunogold particles in aged females compared to young females, in both groups E treatment increased synaptic ERβ-ir.

Similar articles

Cited by

References

    1. Adams MM, Morrison JH, Gore AC. N-methyl-D-aspartate receptor mRNA levels change during reproductive senescence in the hippocampus of female rats. Exp Neurol. 2001a;170:171–179. - PubMed
    1. Adams MM, Oung T, Morrison JH, Gore AC. Length of postovariectomy interval and age, but not estrogen replacement, regulate N-methyl-D-aspartate receptor mRNA levels in the hippocampus of female rats. Exp Neurol. 2001b;170:345–356. - PubMed
    1. Adams MM, Shah RA, Janssen WG, Morrison JH. Diiferent modes of hippocampal plasticity in response to estrogen in young and aged female rats. Proc Natl Acad Sci U S A. 2001c;98:8071–8076. - PMC - PubMed
    1. Adams MM, Fink SE, Janssen WG, Shah RA, Morrison JH. Estrogen modulates synaptic N-methyl-D-aspartate receptor subunit distribution in the aged hippocampus. J Comp Neurol. 2004a;474:419–426. - PubMed
    1. Adams MM, Fink SE, Janssen WG, Shah RA, Morrison JH. Estrogen modulates synaptic N-methyl-D-aspartate receptor subunit distribution in the aged hippocampus. J Comp Neurol. 2004b;474:419–426. - PubMed

Publication types

MeSH terms

Substances

Grants and funding

LinkOut - more resources