Estrogen Alters Hippocampal Dendritic Spine Shape and Enhances Synaptic Protein Immunoreactivity and Spatial Memory in Female Mice

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...

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Published in:	Proceedings of the National Academy of Sciences - PNAS 2004-02, Vol.101 (7), p.2185-2190
Main Authors:	Li, Chenjian, 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.
Format:	Article
Language:	eng
Subjects:	Animal memory Animals Antibodies Behavioral neuroscience Biological Sciences Biomarkers - analysis Brain Dendrites Dendrites - drug effects Dendrites - physiology Dendritic spines Estrogens Estrogens - pharmacology Female Females Hippocampus Hippocampus - cytology Hippocampus - drug effects Hippocampus - physiology Immunohistochemistry Legal objections Memory Memory - drug effects Memory - physiology Mice Mice, Inbred BALB C Mice, Inbred C57BL Microfilament Proteins - metabolism Nerve Tissue Proteins - metabolism Neurology Neurons Ovariectomy Presynaptic Terminals - drug effects Presynaptic Terminals - metabolism Proteins Rodents Space Perception - drug effects Synapses Synapses - drug effects Synapses - metabolism
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Summary:	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 F1hybrids, 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.
ISSN:	0027-8424 1091-6490