ArticleGlia2014
Mechanism of raloxifene-induced upregulation of glutamate transporters in rat primary astrocytes.
Article in Glia, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
47 citing papers in PubMed, 81 citations in OpenAlex.
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- Sex-Specific Properties of Astrocytes: From Development to Evolutionary Insights.Neurochemical research · 2025Review
- G-Protein-Coupled Estrogen Receptor 1 (GPER1) Activation Mitigates Haloperidol-Induced Neurotoxicity in SHSY-5Y Cells and Improves Motor Functions in Adult Zebrafish.Neurochemical research · 2025Article
- Tamoxifen attenuates manganese-induced dysregulation of neuronal REST via the genomic ER-Frontiers in molecular neuroscience · 2025Article
- Microglial dynamics and emerging therapeutic strategies in CNS homeostasis and pathology.Frontiers in pharmacology · 2025Review
- Raloxifene Protects Oxygen-Glucose-Deprived Astrocyte Cells Used to Mimic Hypoxic-Ischemic Brain Injury.International journal of molecular sciences · 2024Article
- Excitotoxic Storms of Ischemic Stroke: A Non-neuronal Perspective.Molecular neurobiology · 2024Review
- Modeling disrupted synapse formation in wolfram syndrome using hESCs-derived neural cells and cerebral organoids identifies Riluzole as a therapeutic molecule.Molecular psychiatry · 2023Article
- A Medicinal Chemistry Perspective on Excitatory Amino Acid Transporter 2 Dysfunction in Neurodegenerative Diseases.Journal of medicinal chemistry · 2023Review
- Aryl Hydrocarbon Receptor in Glia Cells: A Plausible Glutamatergic Neurotransmission Orchestrator.Neurotoxicity research · 2023Review
- Novel EAAT2 activators improve motor and cognitive impairment in a transgenic model of Huntington's disease.Frontiers in behavioral neuroscience · 2023Article
- High-fat diet induces depression-like phenotype via astrocyte-mediated hyperactivation of ventral hippocampal glutamatergic afferents to the nucleus accumbens.Molecular psychiatry · 2022Article
- Tibolone Pre-Treatment Ameliorates the Dysregulation of Protein Translation and Transport Generated by Palmitic Acid-Induced Lipotoxicity in Human Astrocytes: A Label-Free MS-Based Proteomics and Network Analysis.International journal of molecular sciences · 2022Article
- Mechanisms of manganese-induced neurotoxicity and the pursuit of neurotherapeutic strategies.Frontiers in pharmacology · 2022Review
- Peripheral and Central Glutamate Dyshomeostasis in Neurodegenerative Disorders.Current neuropharmacology · 2021Article
- Critical Involvement of Glial Cells in Manganese Neurotoxicity.BioMed research international · 2021Review
- Activation of p38 MAPK participates in the sulbactam-induced cerebral ischemic tolerance mediated by glial glutamate transporter-1 upregulation in rats.Scientific reports · 2020Article
- Tibolone Ameliorates the Lipotoxic Effect of Palmitic Acid in Normal Human Astrocytes.Neurotoxicity research · 2020Article
- Review
- Neuroprotective Effects of Emodin against Ischemia/Reperfusion Injury through Activating ERK-1/2 Signaling Pathway.International journal of molecular sciences · 2020Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Raloxifene (RX), a selective estrogen receptor modulator (SERM), exerts neuroprotection in multiple clinical and experimental settings. Astrocytic glutamate transporters GLT-1 (EAAT2) and GLAST (EAAT1) are the main glutamate transporters in the central nervous system, taking up most of excess glutamate from the synaptic cleft to prevent excitotoxic neuronal death. Since drugs targeting astrocytic glutamate transporters to enhance their expression and function represent potential therapeutics for neurodegenerative disorders associated with excitotoxicity, we tested if RX modulates the expression and function of GLT-1 and GLAST in rat primary astrocytes. The results showed that RX significantly increased glutamate uptake and expression of GLT-1 mRNA and protein levels. RX enhanced GLT-1 expression by the activation of multiple signaling pathways including ERK, EGFR, and CREB mediated by estrogen receptors (ERs) ER-α, ER-β, and GPR30. At the transcriptional level, NF-κB played a critical role in RX-induced GLT-1 expression as RX increased NF-κB reporter activity and induced binding of NF-κB p65 and p50 to the GLT-1 promoter. RX attenuated the reduction of GLT-1 expression and glutamate uptake induced by manganese (Mn) whose chronic high levels of exposure cause manganism. RX also upregulated GLAST by increasing its promoter activity and protein levels via the NF-κB pathway and ERs. Our findings provide new insight into the mechanism of RX-induced enhancement of GLT-1 and GLAST expression, as well as the attenuation of Mn-reduced expression of these transporters. These findings will be highly valuable for developing therapeutics of neurodegenerative diseases associated with impaired astrocytic glutamate transporters.
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Registered trials
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.