ArticleCNS neuroscience & therapeutics2019
GPR30-mediated estrogenic regulation of actin polymerization and spatial memory involves SRC-1 and PI3K-mTORC2 in the hippocampus of female mice.
Article in CNS neuroscience & therapeutics, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 30 citations in OpenAlex.
- Endocrine therapy resistance of breast cancer: Important role of G protein-coupled estrogen receptor (GPER) and new therapeutic strategies.Genes & diseases · 2026Review
- Potential Roles of G Protein-Coupled Receptor 30 (GPR30) in Migraine Pathophysiology.Journal of pain research · 2026Review
- GPR30 Inhibits Neuronal Apoptosis After Subarachnoid Hemorrhage by Activating the Wnt/β-Catenin Pathway in a m6A-dependent Manner.Molecular neurobiology · 2025Article
- The effect of AKT inhibition in α-synuclein-dependent neurodegeneration.Frontiers in molecular neuroscience · 2025Article
- The multifaceted therapeutic value of targeting steroid receptor coactivator-1 in tumorigenesis.Cell & bioscience · 2024Review
- The mTORC2 signaling network: targets and cross-talks.The Biochemical journal · 2024Review
- GPER: An Estrogen Receptor Key in Metastasis and Tumoral Microenvironments.International journal of molecular sciences · 2023Review
- PJA1 mediates the effects of astrocytic GPR30 on learning and memory in female mice.The Journal of clinical investigation · 2023Article
- Deciphering the Influence of Estradiol and Estrogen Receptors on Cognitive Function: A Bibliometric Analysis and Emerging Research Trends.Medical science monitor : international medical journal of experimental and clinical research · 2023Article
- Emerging Evidence on Membrane Estrogen Receptors as Novel Therapeutic Targets for Central Nervous System Pathologies.International journal of molecular sciences · 2023Review
- The effects of GPER on age-associated memory impairment induced by decreased estrogen levels.Frontiers in molecular biosciences · 2023Review
- Transcriptomic Profile Identifies Hippocampal Sgk1 as the Key Mediator of Ovarian Estrogenic Regulation on Spatial Learning and Memory and Aβ Accumulation.Neurochemical research · 2022Article
- Anodal transcranial direct current stimulation alleviates cognitive impairment in an APP/PS1 model of Alzheimer's disease in the preclinical stage.Neural regeneration research · 2022Article
- Steroid receptor coactivator-1: The central intermediator linking multiple signals and functions in the brain and spinal cord.Genes & diseases · 2022Review
- Identification of intelligence-related proteins through a robust two-layer predictor.Communicative & integrative biology · 2022Article
- Treadmill Exercise Reverses the Change of Dendritic Morphology and Activates BNDF-mTOR Signaling Pathway in the Hippocampus and Cerebral Cortex of Ovariectomized Mice.Journal of molecular neuroscience : MN · 2021Article
- Hippocampal Aromatase Knockdown Aggravates Ovariectomy-Induced Spatial Memory Impairment, Aβ Accumulation and Neural Plasticity Deficiency in Adult Female Mice.Neurochemical research · 2021Article
- Estrogen receptors α, β and GPER in the CNS and trigeminal system - molecular and functional aspects.The journal of headache and pain · 2020Article
- The Role of Estrogen in Anxiety-Like Behavior and Memory of Middle-Aged Female Rats.Frontiers in endocrinology · 2020Article
- Soy Isoflavones Accelerate Glial Cell MigrationFrontiers in endocrinology · 2020Article
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aimsThe G-protein-coupled estrogen receptor GPR30 (also referred to as GPER) has been implicated in the estrogenic regulation of hippocampal plasticity and spatial memory; however, the molecular mechanisms are largely unclear.
methodsIn this study, we initially examined the levels of GPR30 in the hippocampus of postnatal, ovariectomy (OVX)- and letrozole (LET)-treated female mice. Under G1, G15, and/or OVX treatment, the spatial memory, spine density, levels of ERα, ERβ, and SRC-1, selected synaptic proteins, mTORC2 signals (Rictor and p-AKT Ser473), and actin polymerization dynamics were subsequently evaluated. Furthermore, G1, G15, and/or E2 combined with SRC-1 and/or PI3K inhibitors, actin cytoskeleton polymerization modulator JPK, and CytoD treatments were used to address the mechanisms that underlie GPR30 regulation in vitro. Finally, mTORC2 activator A-443654 (A4) was used to explore the role of mTORC2 in GPR30 regulation of spatial memory.
resultsThe results showed that high levels of GPR30 were detected in the adult hippocampus and the levels were downregulated by OVX and LET. OVX induced an impairment of spatial memory, and changes in other parameters previously described were reversed by G1 and mimicked by G15. Furthermore, the E2 effects on SRC-1 and mTORC2 signals, synaptic proteins, and actin polymerization were inhibited by G15, whereas G1 effects on these parameters were inhibited by the blockade of SRC-1 or PI3K; the levels of synaptic proteins were regulated by JPK and CytoD. Importantly, G15-induced actin depolymerization and spatial memory impairment were rescued by mTORC2 activation with A4.
conclusionsTaking together, these results demonstrated that decreased GPR30 induces actin depolymerization through SRC-1 and PI3K/mTORC2 pathways and ultimately impairs learning and memory, indicating its potential role as a therapeutic target against hippocampus-based, E2-related memory impairments.
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