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PMID: 11978836 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S.

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

The Journal of neuroscience : the official journal of the Society for Neuroscience ·Vol. 22 ·No. 9 ·2002-05-01 ·Pages 3608-14

Adams MM, Fink SE, Shah RA, Janssen WG, Hayashi S, Milner TA, McEwen BS, Morrison JH

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.

MeSH Terms
Age Factors Aging/metabolism Animals Cell Compartmentation Cell Surface Extensions/metabolism,ultrastructure Estrogen Receptor alpha Estrogens/pharmacology Female Hippocampus/drug effects,metabolism,ultrastructure Immunohistochemistry Microscopy, Immunoelectron Neuronal Plasticity/drug effects,physiology Ovariectomy Presynaptic Terminals/drug effects,metabolism,ultrastructure Pyramidal Cells/metabolism,ultrastructure Rats Rats, Sprague-Dawley Receptors, Estrogen/metabolism Synaptic Vesicles/metabolism,ultrastructure
Chemicals
Estrogen Receptor alpha Estrogens Receptors, Estrogen
Authors & Affiliations
8 authors, click to expand affiliations / ORCID
Adams Michelle M
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 10029-6574, USA.
Fink Susan E
Shah Ravi A
Janssen William G M
Hayashi Shinji
Milner Teresa A
McEwen Bruce S
Morrison John H
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Article Info
Journal
The Journal of neuroscience : the official journal of the Society for Neuroscience
Abbr.
J Neurosci
ISSN
1529-2401
DOI
20026275
Published
2002-05-01
Pages
3608-14
Language
English
Region
United States
NLM ID
8102140
PMCID
PMC6758372
Subset
IM
Grants
NIA NIH HHS · P01 AG016765 · United States
NIA NIH HHS · P01AG16765 · United States
External Links
PubMed source DOI: 20026275 PMC Full Text View journal details
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