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The Journal of Neuroscience, May 1, 2002, 22(9):3608-3614
Estrogen and Aging Affect the Subcellular Distribution of
Estrogen Receptor- in the Hippocampus of Female Rats
Michelle M.
Adams1,
Susan E.
Fink1,
Ravi A.
Shah1,
William G. M.
Janssen1,
Shinji
Hayashi2,
Teresa A.
Milner3,
Bruce S.
McEwen4, and
John H.
Morrison1
1 Kastor Neurobiology of Aging Laboratories, Fishberg
Research Center for Neurobiology, and Henry L. Schwartz Department of
Geriatrics and Adult Development, Mount Sinai School of Medicine, New
York, New York 10029, 2 Laboratory of Endocrinology,
Graduate School of Integrated Science, Yokohama City University,
Yokohama 236-0027, Japan, 3 Department of Neurology, Weill
Medical College of Cornell University, New York, New York 10021, and
4 Harold and Margaret Milliken Hatch Laboratory of
Neuroendocrinology, The Rockefeller University, New York, New York
10021
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- (ER-) 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- 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- 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--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--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- 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- 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- levels
and its subcellular localization vis-à-vis the synapse. Such a
role for spinous ER- has important implications for age-related attenuation of estrogen-induced hippocampal plasticity.
Key words:
CA1; ovariectomy; postembedding immunogold; electron
microscopy; synaptic plasticity
Copyright © 2002 Society for Neuroscience 0270-6474/02/2293608-07$05.00/0
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