ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2020
Astrocyte-Derived Estrogen Regulates Reactive Astrogliosis and is Neuroprotective following Ischemic Brain Injury.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 80 papers.
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Who cites it
80 citing papers in PubMed, 118 citations in OpenAlex.
- High-Frequency Repetitive Transcranial Magnetic Stimulation Attenuates Post-Stroke Brain Fibrosis by Increasing Brain-Derived Estrogen Levels: A Dual-Tracer PET/CT Study.Molecular neurobiology · 2026Article
- Parenchymal precursor cells act in concert with canonical neural progenitors to facilitate neural circuit recovery following neuronal loss.bioRxiv : the preprint server for biology · 2026Article
- PFOS Impairs Cognitive Function in Female Rats by Disrupting Astrocyte-Derived Estrogen-ERβ-NDRG2 Signaling Axis.Toxics · 2026Article
- Increased expression of aromatase after focal cerebral ischemia: Relevance to neuroprotection and functional recovery.Neuroprotection (Chichester, England) · 2026Article
- Article
- Back Again to the Future: A New Era for Cerebroprotection.Annals of neurology · 2026Review
- Establishment of a novel brainstem ischemic dysphagia model: single-cell sequencing reveals the molecular mechanisms underlying mPES intervention.Journal of neuroengineering and rehabilitation · 2025Article
- Aromatase as a Central Node in Astrocyte Health and Homeostasis.Molecular neurobiology · 2025Review
- Progress and Perspectives on the Estrogen-Microbiota-Brain Axis in Alzheimer's Disease.Neurochemical research · 2025Review
- Ultrastructural Characteristics of the Juvenile Chum Salmon (International journal of molecular sciences · 2025Article
- Extracellular lactate improves neurogenesis by modulating H3K9 lactylation and SnoN expression under hypoxic conditions.Stem cell research & therapy · 2025Article
- Role of astrocytes in the pathogenesis of perinatal brain injury.Molecular medicine (Cambridge, Mass.) · 2025Review
- Gosha-Jinki-Gan Reduces Inflammation in Chronic Ischemic Stroke Mouse Models by Suppressing the Infiltration of Macrophages.Biomolecules · 2025Article
- Estradiol Mediates Astrocyte-Neuron Communication in the Hippocampus.Molecular neurobiology · 2025Article
- Cell Type-Specific Effects ofToxins · 2025Article
- Temporal impact of sepsis on Alzheimer's disease pathology and neuroinflammation.Progress in neurobiology · 2025Article
- The Role of Astrocytes in Poststroke Rehabilitation.Brain and behavior · 2025Review
- The role of estrogen in Alzheimer's disease pathogenesis and therapeutic potential in women.Molecular and cellular biochemistry · 2025Review
- Neuroestrogens, the hippocampus, and female cognitive aging.Hormones and behavior · 2025Review
- Gastrodin inhibits reactive astrocyte-mediated inflammation in hypoxic-ischemic brain damage through S100B/RAGE-Smad3 signaling.Acta biochimica et biophysica Sinica · 2025Article
20 more citing papers are in PubMed but not listed here.
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
Abstract
Expression of the 17β-estradiol (E2) synthesis enzyme aromatase is highly upregulated in astrocytes following brain injury. However, the precise role of astrocyte-derived E2 in the injured brain remains unclear. In the current study, we generated a glial fibrillary acidic protein (GFAP) promoter-driven aromatase knock-out (GFAP-ARO-KO) mouse model to deplete astrocyte-derived E2 in the brain and determine its roles after global cerebral ischemia (GCI) in male and female mice. GFAP-ARO-KO mice were viable and fertile, with normal gross brain structure, normal morphology, intensity and distribution of astrocytes, normal aromatase expression in neurons, and normal cognitive function basally. In contrast, after GCI, GFAP-ARO-KO mice: (1) lacked the normal elevation of astrocyte aromatase and hippocampal E2 levels; (2) had significantly attenuated reactive astrogliosis; and (3) displayed enhanced neuronal damage, microglia activation, and cognitive deficits. RNA-sequencing (RNA-seq) analysis revealed that the ischemic GFAP-ARO-KO mouse hippocampus failed to upregulate the "A2" panel of reactive astrocyte genes. In addition, the JAK-STAT3 pathway, which is critical for the induction of reactive astrogliosis, was significantly downregulated in the GFAP-ARO-KO hippocampus following GCI. Finally, exogenous E2 administration fully rescued the compromised JAK-STAT3 pathway and reactive astrogliosis, and reversed the enhanced neuronal damage and microglial activation in the GFAP-ARO-KO mice after GCI, suggesting that the defects in the KO mice are because of a loss of E2 rather than an increase in precursor androgens. In conclusion, the current study provides novel genetic evidence for a beneficial role of astrocyte-derived E2 in reactive astrogliosis, microglial activation, and neuroprotection following an ischemic injury to the brain.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.