ArticleJournal of neuroinflammation2023
Supraphysiologic doses of 17β-estradiol aggravate depression-like behaviors in ovariectomized mice possibly via regulating microglial responses and brain glycerophospholipid metabolism.
Article in Journal of neuroinflammation, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 22 citations in OpenAlex.
- Metformin Ameliorates Diabetes-Associated Cognitive Dysfunction via p53/Parkin-Mediated Mitophagy.Diabetes, obesity & metabolism · 2026Article
- Engineering RVG-modified exosomes for targeting TGF-β1 signaling in stroke recovery.Journal of translational medicine · 2026Article
- Estrogen Replacement Therapy in Ovariectomized Rats: Complementary Roles of ER and GPR30 in Alleviating Depressive-like Behavior.Current issues in molecular biology · 2026Article
- Medical Treatment for Endometriosis: One Size Does Not Fit All.Journal of clinical medicine · 2026Review
- Disrupted Estrogen Homeostasis Drives Female-Specific Depressive-Like and Anxiety-Like Behaviors via Convergent ERα Downregulation in the Ventral Hippocampus.International journal of biological sciences · 2026Article
- Protective effects of estradiol on neuroinflammation in chronic obstructive pulmonary disease related depression.Journal of thoracic disease · 2025Article
- Mechanism of Microbiota-Gut-Brain in Perimenopausal Depression: An Inflammatory Perspective.Expert reviews in molecular medicine · 2025Review
- Chronic 17β-estradiol treatment improves negative valence, anhedonic profile, and social interactions in ovariectomized, middle-aged female rats.Frontiers in behavioral neuroscience · 2025Article
- The estrogen-brain interface in neuroinflammation: a multidimensional mechanistic insight.Frontiers in aging neuroscience · 2025Review
- Hormonal regulatory networks in spinal cord injury: mechanistic insights, crosstalk, and therapeutic innovations.Frontiers in endocrinology · 2025Review
- Rutin Attenuates Gentamycin-induced Hair Cell Injury in the Zebrafish Lateral Line via Suppressing STAT1.Molecular neurobiology · 2024Article
- Estrogen-immuno-neuromodulation disorders in menopausal depression.Journal of neuroinflammation · 2024Review
- Daphnetin Ameliorates Neuropathic Pain via Regulation of Microglial Responses and Glycerophospholipid Metabolism in the Spinal Cord.Pharmaceuticals (Basel, Switzerland) · 2024Article
- Santacruzamate A Alleviates Pain and Pain-Related Adverse Emotions through the Inhibition of Microglial Activation in the Anterior Cingulate Cortex.ACS pharmacology & translational science · 2024Article
- Review
- Sini San ameliorates lipid metabolism in hyperprolactinemia rat with liver-depression.Current research in food science · 2024Article
- Article
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
background17β-Estradiol (E2) is generally considered neuroprotective in humans. However, the current clinical use of estrogen replacement therapy (ERT) is based on the physiological dose of E2 to treat menopausal syndrome and has limited therapeutic efficacy. The efficacy and potential toxicity of superphysiological doses of ERT for menopausal neurodegeneration are unknown.
methodsIn this study, we investigated the effect of E2 with a supraphysiologic dose (0.5 mg/kg, sE2) on the treatment of menopausal mouse models established by ovariectomy. We performed the open field, Y-maze spontaneous alternation, forced swim tests, and sucrose preference test to investigate behavioral alterations. Subsequently, the status of microglia and neurons was detected by immunohistochemistry, HE staining, and Nissl staining, respectively. Real-time PCR was used to detect neuroinflammatory cytokines in the hippocampus and cerebral cortex. Using mass spectrometry proteomics platform and LC-MS/ MS-based metabolomics platform, proteins and metabolites in brain tissues were extracted and analyzed. BV2 and HT22 cell lines and primary neurons and microglia were used to explore the underlying molecular mechanisms in vitro.
resultssE2 aggravated depression-like behavior in ovariectomized mice, caused microglia response, and increased proinflammatory cytokines in the cerebral cortex and hippocampus, as well as neuronal damage and glycerophospholipid metabolism imbalance. Subsequently, we demonstrated that sE2 induced the pro-inflammatory phenotype of microglia through ERα/NF-κB signaling pathway and downregulated the expression of cannabinoid receptor 1 in neuronal cells, which were important in the pathogenesis of depression.
conclusionThese data suggest that sE2 may be nonhelpful or even detrimental to menopause-related depression, at least partly, by regulating microglial responses and glycerophospholipid metabolism.
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Registered trials
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