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PMID: 14766964 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S.

Estrogen alters hippocampal dendritic spine shape and enhances synaptic protein immunoreactivity and spatial memory in female mice.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 101 ·No. 7 ·2004-02-17 ·Pages 2185-90

Li C, Brake WG, Romeo RD, Dunlop JC, Gordon M, Buzescu R, Magarinos AM, Allen PB, Greengard P, Luine V, McEwen BS

Abstract

Estrogen (E) treatment induces axospinous synapses in rat hippocampus in vivo and in cultured hippocampal neurons in vitro. To better explore the molecular mechanisms underlying this phenomenon, we have established a mouse model for E action in the hippocampus by using Golgi impregnation to examine hippocampal dendritic spine morphology, radioimmunocytochemistry (RICC) and silver-enhanced immunocytochemistry to examine expression levels of synaptic protein markers, and hippocampal-dependent object-placement memory as a behavioral readout for the actions of E. In ovariectomized mice of several strains and F(1) hybrids, the total dendritic spine density on neurons in the CA1 region was not enhanced by E treatment, a finding that differs from that in the female rat. E treatment of ovariectomized C57BL/6J mice, however, caused an increase in the number of spines with mushroom shapes. By RICC and silver-enhanced immunocytochemistry, we found that the immunoreactivity of postsynaptic markers (PSD95 and spinophilin) and a presynaptic marker (syntaxin) were enhanced by E treatment throughout all fields of the dorsal hippocampus. In the object-placement tests, E treatment enhanced performance of object placement, a spatial episodic memory task. Taken together, the morphology and RICC results suggest a previously uncharacterized role of E in synaptic structural plasticity that may be interpreted as a facilitation of the spine-maturation process and may be associated with enhancement of hippocampal-dependent memory.

MeSH Terms
Animals Biomarkers/analysis Dendrites/drug effects,physiology Estrogens/pharmacology Female Hippocampus/cytology,drug effects,physiology Immunohistochemistry Memory/drug effects,physiology Mice Mice, Inbred BALB C Mice, Inbred C57BL Microfilament Proteins/metabolism Nerve Tissue Proteins/metabolism Ovariectomy Presynaptic Terminals/drug effects,metabolism Space Perception/drug effects Synapses/drug effects,metabolism
Chemicals
Biomarkers Estrogens Microfilament Proteins Nerve Tissue Proteins neurabin
Authors & Affiliations
11 authors, click to expand affiliations / ORCID
Li Chenjian
Department of Neurology and Neuroscience, Weill Medical College of Cornell University, New York, NY 10021, USA. [email protected]
Brake Wayne G
Romeo Russell D
Dunlop John C
Gordon Marisa
Buzescu Rodica
Magarinos Ana Maria
Allen Patrick B
Greengard Paul
Luine Victoria
McEwen Bruce S
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.0307313101
Email
[email protected]
Published
2004-02-17
Epub
2004-00-06
Pages
2185-90
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC357073
Subset
IM
Grants
NIGMS NIH HHS · S06 GM060654 · United States
NINDS NIH HHS · R01 NS007080 · United States
NIMH NIH HHS · P01 MH040899 · United States
NIGMS NIH HHS · GM60654 · United States
NIDA NIH HHS · DA-10004 · United States
NINDS NIH HHS · F32 NS010492 · United States
NIMH NIH HHS · MH-40899 · United States
NINDS NIH HHS · NS-07080 · United States
NINDS NIH HHS · NS10492 · United States
NIDA NIH HHS · P01 DA010044 · United States
External Links
PubMed source DOI: 10.1073/pnas.0307313101 PMC Full Text View journal details
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