Open AccessNuclear and membrane estrogen receptor antagonists induce similar mTORC 2 activation‐reversible changes in synaptic protein expression and actin polymerization in the mouse hippocampus
Author(s) -
Xing FangZhou,
Zhao YanGang,
Zhang YuanYuan,
He Li,
Zhao JiKai,
Liu MengYing,
Liu Yan,
Zhang JiQiang
Publication year - 2018
Publication title -
cns neuroscience and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.403
H-Index - 69
eISSN - 1755-5949
pISSN - 1755-5930
DOI - 10.1111/cns.12806
Subject(s) - synaptophysin , synaptic plasticity , microbiology and biotechnology , actin cytoskeleton , cofilin , biology , dendritic spine , hippocampal formation , chemistry , endocrinology , receptor , cytoskeleton , biochemistry , immunology , immunohistochemistry , cell
Summary Aims Estrogens play pivotal roles in hippocampal synaptic plasticity through nuclear receptors ( nER s; including ER α and ER β) and the membrane receptor ( mER ; also called GPR 30), but the underlying mechanism and the contributions of nER s and mER remain unclear. Mammalian target of rapamycin complex 2 ( mTORC 2) is involved in actin cytoskeleton polymerization and long‐term memory, but whether mTORC 2 is involved in the regulation of hippocampal synaptic plasticity by ER s is unclear. Methods We treated animals with nER antagonists ( MPP / PHTPP ) or the mER antagonist (G15) alone or in combination with A‐443654, an activator of mTORC 2. Then, we examined the changes in hippocampal SRC ‐1 expression, mTORC 2 signaling (rictor and phospho‐ AKTS er473), actin polymerization (phospho‐cofilin and profilin‐1), synaptic protein expression (GluR1, PSD 95, spinophilin, and synaptophysin), CA 1 spine density, and synapse density. Results All of the examined parameters except synaptophysin expression were significantly decreased by MPP / PHTPP and G15 treatment. MPP / PHTPP and G15 induced a similar decrease in most parameters except p‐cofilin, GluR1, and spinophilin expression. The ER antagonist‐induced decreases in these parameters were significantly reversed by mTORC 2 activation, except for the change in SRC ‐1, rictor, and synaptophysin expression. Conclusions nER s and mER contribute similarly to the changes in proteins and structures associated with synaptic plasticity, and mTORC 2 may be a novel target of hippocampal‐dependent dementia such as Alzheimer's disease as proposed by previous studies.