Estrogen and aging affect the subcellular distribution of estrogen receptor-alpha in the hippocampus of female rats - PubMed (original) (raw)

Estrogen and aging affect the subcellular distribution of estrogen receptor-alpha in the hippocampus of female rats

Michelle M Adams et al. J Neurosci. 2002.

Abstract

Estrogen replacement increases both the number of dendritic spines and the density of axospinous synapses in the hippocampal CA1 region in young rats, yet this is attenuated in aged rats. The estrogen receptor-alpha (ER-alpha) is localized within select spines of CA1 pyramidal cells in young animals and thus may be involved locally in this process. The present study investigated the effects of estrogen on the ultrastructural distribution of ER-alpha in the CA1 of young (3-4 months) and aged (22-23 months) Sprague Dawley rats using postembedding immunogold electron microscopy. Within dendritic spines, most ER-alpha immunoreactivity (IR) was seen in plasmalemmal and cytoplasmic regions of spine heads, with a smaller proportion within 60 nm of the postsynaptic density. In presynaptic terminals, ER-alpha-IR was clustered and often associated with synaptic vesicles. Significant effects of both aging and estrogen were observed. Quantitative analysis revealed that nonsynaptic pools of ER-alpha-IR within the presynaptic and postsynaptic compartments were decreased (35 and 27%, respectively) in the young estrogen-replaced animals compared with those that received vehicle. Such localized regulation of ER-alpha in response to circulating estrogen levels might directly affect synaptic signaling in CA1 pyramidal cells. No estrogen treatment-related differences were observed in the aged animals. However, 50% fewer spines contained ER-alpha in the aged compared with young hippocampus. These data suggest that the decreased responsiveness of hippocampal synapses to estrogen in aged animals may result from age-related decrements in ER-alpha levels and its subcellular localization vis-à-vis the synapse. Such a role for spinous ER-alpha has important implications for age-related attenuation of estrogen-induced hippocampal plasticity.

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Figures

Fig. 1.

Fig. 1.

Distribution of ER-α-IR within axospinous synapses in the stratum radiatum of the hippocampal CA1 region. Gold particles were observed to be localized both presynaptically (A) and postsynaptically (B, C). In the axon terminal (A), gold particles were associated with small synaptic vesicles. In dendritic spines, gold particles were found within the head of the spine (B, C) and affiliated within the postsynaptic density. Particles within the postsynaptic density were usually found in the more lateral portion.ax, Axon; sp, spine. Scale bar, 100 nm.

Fig. 2.

Fig. 2.

Percentage of ER-α-IR-labeled synapses in young and aged rats. The graphs illustrate that the percentage of ER-α-IR synapses decreases (50%) with age (*p < 0.0001); however, there is no effect of estrogen treatment in either group (both _p_ values > 0.31).n = 10 for each age group. OVX, Ovariectomized; E 2, estrogen-treated;Veh, vehicle-treated.

Fig. 3.

Fig. 3.

Levels of ER-α-IR per synapse in young and aged vehicle-treated (Veh) and estrogen-treated (E 2) rats. The amount of ER-α-IR particles per synapse in young rats significantly decreases with estrogen treatment compared with vehicle both presynaptically (A) and postsynaptically (B) (*both p values < 0.05). No differences were observed in the estrogen- and vehicle-treated aged groups (both _p_ values > 0.16).n = 5 for each treatment group. OVX, Ovariectomized.

Fig. 4.

Fig. 4.

Schematic diagram illustrating the proposed mechanisms of estrogen-induced plasticity of ER-α in young (A) and aged (B) animals. Estrogen treatment either decreases the amount of ER-α per synapse in young animals or leads to a redistribution of the receptor resulting from the formation of new dendritic spines and alterations in presynaptic terminal shape. ER-α levels are unchanged in aged animals in both presynaptic and postsynaptic compartments, but there is an overall decrease in the percentage of terminals that express ER-α-IR. Small black dots represent immunogold particles labeling ER-α, open circles represent synaptic vesicles, and the gray zones represent the postsynaptic density.

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References

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