ArticleJournal of neuroinflammation2021
Prostaglandin EP2 receptor antagonist ameliorates neuroinflammation in a two-hit mouse model of Alzheimer's disease.
Article in Journal of neuroinflammation, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 12 citations in OpenAlex.
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- Novel EP2 Antagonist Attenuates Microgliosis and Memory Deficits in Pilocarpine-Induced Status Epilepticus Mice.Journal of medicinal chemistry · 2026Article
- ShenQi DiHuang Decoction (SQDHD) Ameliorates Neuroinflammation and Neuropsychiatric Manifestations in Pristane Induced Lupus Mice via Blocking JAK1-STAT3 Pathway.CNS neuroscience & therapeutics · 2026Article
- The potential role of COX-2/PGs signaling pathway in epileptogenesis and associated neuroinflammation: collusions or serendipity.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2026Review
- Antagonism of the EP2 Receptor Reveals Sex-Specific Protection in a Two-Hit Mouse Model of Alzheimer's Disease.ACS chemical neuroscience · 2026Article
- Genetic Variation and Ultrafiltration with Peritoneal Dialysis: A Genome-Wide Association Study.Journal of the American Society of Nephrology : JASN · 2026Article
- Neuroinflammation and Disease: Pathways and Opportunities.Annual review of pharmacology and toxicology · 2026Review
- Monoterpene-rich essential oil fromToxicology research · 2025Article
- [Effects of hyperoxia on the expression of hippocampal N-methyl D-aspartate receptor 1 and its synapse-associated molecules in neonatal rats].Zhongguo dang dai er ke za zhi = Chinese journal of contemporary pediatrics · 2025Article
- Prostaglandins in the Inflamed Central Nervous System: Potential Therapeutic Targets.Current drug targets · 2024Review
- Targeting EP2 Receptor for Drug Discovery: Strengths, Weaknesses, Opportunities, and Threats (SWOT) Analysis.Journal of medicinal chemistry · 2023Review
- Preclinical development of an EP2 antagonist for post-seizure cognitive deficits.Neuropharmacology · 2023Article
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7 authors at 1 institution in 1 country.
Funding
Abstract
backgroundAlzheimer's disease (AD) causes substantial medical and societal burden with no therapies ameliorating cognitive deficits. Centralized pathologies involving amyloids, neurofibrillary tangles, and neuroinflammatory pathways are being investigated to identify disease-modifying targets for AD. Cyclooxygenase-2 (COX-2) is one of the potential neuroinflammatory agents involved in AD progression. However, chronic use of COX-2 inhibitors in patients produced adverse cardiovascular effects. We asked whether inhibition of EP2 receptors, downstream of the COX-2 signaling pathway, can ameliorate neuroinflammation in AD brains in presence or absence of a secondary inflammatory stimuli.
methodsWe treated 5xFAD mice and their non-transgenic (nTg) littermates in presence or absence of lipopolysaccharide (LPS) with an EP2 antagonist (TG11-77.HCl). In cohort 1, nTg (no-hit) or 5xFAD (single-hit-genetic) mice were treated with vehicle or TG11-77.HCl for 12 weeks. In cohort 2, nTg (single-hit-environmental) and 5xFAD mice (two-hit) were administered LPS (0.5 mg/kg/week) and treated with vehicle or TG11-77.HCl for 8 weeks.
resultsComplete blood count analysis showed that LPS induced anemia of inflammation in both groups in cohort 2. There was no adverse effect of LPS or EP2 antagonist on body weight throughout the treatment. In the neocortex isolated from the two-hit cohort of females, but not males, the elevated mRNA levels of proinflammatory mediators (IL-1β, TNF, IL-6, CCL2, EP2), glial markers (IBA1, GFAP, CD11b, S110B), and glial proteins were significantly reduced by EP2 antagonist treatment. Intriguingly, the EP2 antagonist had no effect on either of the single-hit cohorts. There was a modest increase in amyloid-plaque deposition upon EP2 antagonist treatment in the two-hit female brains, but not in the single-hit genetic female cohort.
conclusionThese results reveal a potential neuroinflammatory role for EP2 in the two-hit 5xFAD mouse model. A selective EP2 antagonist reduces inflammation only in female AD mice subjected to a second inflammatory insult.
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