ArticleFrontiers in molecular neuroscience2023
Roxadustat (FG-4592) abated lipopolysaccharides-induced depressive-like symptoms
Article in Frontiers in molecular neuroscience, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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Who cites it
8 citing papers in PubMed, 15 citations in OpenAlex.
- The adiponectin-depression nexus: a brief review of mechanisms and therapeutic opportunities.Metabolic brain disease · 2026Review
- Computational biological analysis reveals that HIF-1 and FoxO signaling pathways influence cognitive impairment in patients with depression.Translational psychiatry · 2025Article
- FG-4592 combined with PRP significantly accelerates the healing of refractory diabetic wounds by upregulating HIF-1α.Scientific reports · 2025Article
- Pentoxifylline Prevents Neuroinflammation and Modifies PTEN/TrkB Signaling in an LPS-Induced Depression Model.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2025Article
- PKR Inhibition Prevents Neuroinflammation and Rescues Depressive-Like Behaviors via BDNF/TrkB Signaling.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2025Article
- ApoE4 dysregulation incites depressive symptoms and mitochondrial impairments in mice.Journal of cellular and molecular medicine · 2024Article
- Bmal1 haploinsufficiency impairs fear memory and modulates neuroinflammation via the 5-HT2C receptor.Frontiers in pharmacology · 2024Article
- Systems biology approaches to identify potential targets and inhibitors of the intestinal microbiota to treat depression.Scientific reports · 2023Article
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Authors and funding
12 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Background: Despite its role in inflammation and the redox system under hypoxia, the effects and molecular mechanisms of hypoxia-inducible factor (HIF) in neuroinflammation-associated depression are poorly explored. Furthermore, Prolyl hydroxylase domain-containing proteins (PHDs) regulate HIF-1; however, whether and how PHDs regulate depressive-like behaviors under Lipopolysaccharides (LPS)-induced stress conditions remain covered. Methods: To highlight the roles and underlying mechanisms of PHDs-HIF-1 in depression, we employed behavioral, pharmacological, and biochemical analyses using the LPS-induced depression model. Results: Lipopolysaccharides treatment induced depressive-like behaviors, as we found, increased immobility and decreased sucrose preference in the mice. Concurrently, we examined increased cytokine levels, HIF-1 expression, mRNA levels of PHD1/PHD2, and neuroinflammation upon LPS administration, which Roxadustat reduced. Furthermore, the PI3K inhibitor wortmannin reversed Roxadustat-induced changes. Additionally, Roxadustat treatment attenuated LPS-induced synaptic impairment and improved spine numbers, ameliorated by wortmannin. Conclusion: Lipopolysaccharides-dysregulates HIF-PHDs signaling may contribute to neuroinflammation-coincides depression
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