Dataset Information

Roxadustat (FG-4592) abated lipopolysaccharides-induced depressive-like symptoms via PI3K signaling.

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 via PI3K signaling.

SUBMITTER: Li A

PROVIDER: S-EPMC10056220 | biostudies-literature | 2023

REPOSITORIES: biostudies-literature

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Roxadustat (FG-4592) abated lipopolysaccharides-induced depressive-like symptoms <i>via</i> PI3K signaling.

Li Axiang A Liu Zizhen Z Ali Tahir T Gao Ruyan R Luo Yanhua Y Gong Qichao Q Zheng Chenyou C Li Weifen W Guo Hongling H Liu Xinshe X Li Shupeng S Li Tao T

Frontiers in molecular neuroscience 20230315

<h4>Background</h4>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.<h4>Methods</h4>To highlight the roles and underlying mec ...[more]

PMID: 37008780

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