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 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.
Li
Chenjian
C
Department of Neurology and Neuroscience, Weill Medical College of Cornell University, New York, NY 10021, USA. chl2011@med.cornell.edu
Brake
Wayne G
WG
Romeo
Russell D
RD
Dunlop
John C
JC
Gordon
Marisa
M
Buzescu
Rodica
R
Magarinos
Ana Maria
AM
Allen
Patrick B
PB
Greengard
Paul
P
Luine
Victoria
V
McEwen
Bruce S
BS
D000818:Animals; D015415:Biomarkers / Q000032:analysis; D003712:Dendrites / Q000187:drug effects* / Q000502:physiology; D004967:Estrogens / Q000494:pharmacology*; D005260:Female; D006624:Hippocampus / Q000166:cytology* / Q000187:drug effects* / Q000502:physiology; D007150:Immunohistochemistry; D008568:Memory / Q000187:drug effects* / Q000502:physiology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008840:Microfilament Proteins / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000378:metabolism; D010052:Ovariectomy; D017729:Presynaptic Terminals / Q000187:drug effects / Q000378:metabolism; D013028:Space Perception / Q000187:drug effects*; D013569:Synapses / Q000187:drug effects* / Q000378:metabolism; D000099273:Neurabins
D015415:Biomarkers; D004967:Estrogens; D008840:Microfilament Proteins; D009419:Nerve Tissue Proteins; D000099273:Neurabins