Fang-Zhou Xing1, Yan-Gang Zhao2, Yuan-Yuan Zhang2, Li He3, Ji-Kai Zhao2, Meng-Ying Liu2, Yan Liu1, Ji-Qiang Zhang2. 1. Key Laboratory of Freshwater Fish Reproduction and Development (Ministry of Education), Key Laboratory of Aquatic Science of Chongqing, Key Laboratory of Eco-environments in Three Gorges Reservoir Region, School of Life Sciences, Southwest University, Chongqing, China. 2. Department of Neurobiology, Third Military Medical University, Chongqing, China. 3. School of Nursing, Third Military Medical University, Chongqing, China.
Abstract
AIMS: Estrogens play pivotal roles in hippocampal synaptic plasticity through nuclear receptors (nERs; including ERα and ERβ) and the membrane receptor (mER; also called GPR30), but the underlying mechanism and the contributions of nERs and mER remain unclear. Mammalian target of rapamycin complex 2 (mTORC2) is involved in actin cytoskeleton polymerization and long-term memory, but whether mTORC2 is involved in the regulation of hippocampal synaptic plasticity by ERs 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 mTORC2. Then, we examined the changes in hippocampal SRC-1 expression, mTORC2 signaling (rictor and phospho-AKTSer473), actin polymerization (phospho-cofilin and profilin-1), synaptic protein expression (GluR1, PSD95, spinophilin, and synaptophysin), CA1 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 mTORC2 activation, except for the change in SRC-1, rictor, and synaptophysin expression. CONCLUSIONS: nERs and mER contribute similarly to the changes in proteins and structures associated with synaptic plasticity, and mTORC2 may be a novel target of hippocampal-dependent dementia such as Alzheimer's disease as proposed by previous studies.
AIMS: Estrogens play pivotal roles in hippocampal synaptic plasticity through nuclear receptors (nERs; including ERα and ERβ) and the membrane receptor (mER; also called GPR30), but the underlying mechanism and the contributions of nERs and mER remain unclear. Mammalian target of rapamycin complex 2 (mTORC2) is involved in actin cytoskeleton polymerization and long-term memory, but whether mTORC2 is involved in the regulation of hippocampal synaptic plasticity by ERs 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 mTORC2. Then, we examined the changes in hippocampal SRC-1 expression, mTORC2 signaling (rictor and phospho-AKTSer473), actin polymerization (phospho-cofilin and profilin-1), synaptic protein expression (GluR1, PSD95, spinophilin, and synaptophysin), CA1 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 mTORC2 activation, except for the change in SRC-1, rictor, and synaptophysin expression. CONCLUSIONS: nERs and mER contribute similarly to the changes in proteins and structures associated with synaptic plasticity, and mTORC2 may be a novel target of hippocampal-dependent dementia such as Alzheimer's disease as proposed by previous studies.
Authors: Wayne R Hawley; Elin M Grissom; Nicole M Moody; Gary P Dohanich; Nandini Vasudevan Journal: Behav Brain Res Date: 2014-01-18 Impact factor: 3.332
Authors: Chenjian Li; Wayne G Brake; Russell D Romeo; John C Dunlop; Marisa Gordon; Rodica Buzescu; Ana Maria Magarinos; Patrick B Allen; Paul Greengard; Victoria Luine; Bruce S McEwen Journal: Proc Natl Acad Sci U S A Date: 2004-02-06 Impact factor: 11.205
Authors: Nathalie Sumien; J Thomas Cunningham; Delaney L Davis; Rachel Engelland; Oluwadarasimi Fadeyibi; George E Farmer; Steve Mabry; Paapa Mensah-Kane; Oanh T P Trinh; Philip H Vann; E Nicole Wilson; Rebecca L Cunningham Journal: Endocrinology Date: 2021-11-01 Impact factor: 5.051