ArticleThe Journal of clinical investigation2023
PJA1 mediates the effects of astrocytic GPR30 on learning and memory in female mice.
Article in The Journal of clinical investigation, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed.
- Article
- Estradiol and Raloxifene Protect Ovariectomized Mice from Acute Kidney Injury via G Protein-Coupled Estrogen Receptor-Mediated Nuclear Factor Erythroid 2-Related Factor 2/Heme Oxygenase-1 Activation.International journal of molecular sciences · 2026Article
- Mechanistic insights into taxane-induced psychiatric adverse events: a global pharmacovigilance and experimental investigation.Molecular psychiatry · 2026Article
- SerpinA3N-APOE interaction in astrocytes exacerbates Alzheimer's disease progression through NFκB activation.Journal of neuroinflammation · 2025Article
- Astrocytes as Active Participants in Memory.Journal of neurochemistry · 2025Review
- The E3 Ubiquitin Ligase PRAJA1: A Key Regulator of Synaptic Dynamics and Memory Processes with Implications for Alzheimer's Disease.International journal of molecular sciences · 2025Article
- The GPR30 agonist G-1 promotes hair growth via Wnt/Hedgehog signaling in mice.Frontiers in pharmacology · 2025Article
- Activation of GPER1 by G1 prevents PTSD-like behaviors in mice: Illustrating the mechanisms from BDNF/TrkB to mitochondria and synaptic connection.CNS neuroscience & therapeutics · 2024Article
- Estrogen-immuno-neuromodulation disorders in menopausal depression.Journal of neuroinflammation · 2024Review
- Restoring periodontal tissue homoeostasis prevents cognitive decline by reducing the number of Serpina3nInnovation (Cambridge (Mass.)) · 2024Article
Corrections and comments
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Authors and funding
19 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Hormone replacement therapy (HRT) is not recommended for treating learning and memory decline in menopausal women because it exerts adverse effects by activating classic estrogen receptors ERα and ERβ. The membrane estrogen receptor G protein-coupled receptor 30 (GPR30) has been reported to be involved in memory modulation; however, the underlying mechanisms are poorly understood. Here, we found that GPR30 deletion in astrocytes, but not in neurons, impaired learning and memory in female mice. Astrocytic GPR30 depletion induced A1 phenotype transition, impairing neuronal function. Further exploration revealed that Praja1 (PJA1), a RING ubiquitin ligase, mediated the effects of astrocytic GPR30 on learning and memory by binding to Serpina3n, which is a molecular marker of neuroinflammation in astrocytes. GPR30 positively modulated PJA1 expression through the CREB signaling pathway in cultured murine and human astrocytes. Additionally, the mRNA levels of GPR30 and PJA1 were reduced in exosomes isolated from postmenopausal women while Serpina3n levels were increased in the plasma. Together, our findings suggest a key role for astrocytic GPR30 in the learning and memory abilities of female mice and identify GPR30/PJA1/Serpina3n as potential therapeutic targets for learning and memory loss in peri- and postmenopausal women.
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