In:
CNS Neuroscience & Therapeutics, Wiley, Vol. 24, No. 6 ( 2018-06), p. 495-507
Abstract:
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.
Type of Medium:
Online Resource
ISSN:
1755-5930
,
1755-5949
DOI:
10.1111/cns.2018.24.issue-6
Language:
English
Publisher:
Wiley
Publication Date:
2018
detail.hit.zdb_id:
2423467-9
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