ArticleInflammation2025
Ghrelin Inhibits Inflammasomes Activation in Astrocytes, Alleviates Pyroptosis, and Prevents Lipopolysaccharide-induced Depression-like Behavior in Mice.
Article in Inflammation, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers, 1 of them a synthesis that pooled it.
What it found
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Who cites it
5 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Natural antidepressants in neuroimmunomodulation: molecular mechanisms, action targets, and therapeutic potential.Frontiers in immunology · 2025Pooled it
- Integrative role of orexigenic peptides in neuroprotection and neurodegenerative disease modulation.Bioscience reports · 2026Review
- Forsythoside A Alleviates Neuroinflammatory Damage via Inhibiting TLR4/NF-κB/NLRP3 Activation-Induced Astrocyte Pyroptosis in Cerebral Ischemia-Reperfusion.CNS neuroscience & therapeutics · 2026Article
- Article
- Cell death pathways in the pathogenesis of depression: mechanisms and therapeutic implications.Frontiers in cell and developmental biology · 2026Review
Corrections and comments
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Authors and funding
7 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Depression is the leading cause of disability worldwide and places a significant burden on society. Neuroinflammation is closely associated with the pathophysiology of depression. Increasing evidence suggests that astrocytes, as the most abundant glial cells in the brain, are involved in the occurrence and development of depression due to morphological abnormalities and dysfunction. Astrocytes express the NOD-like receptor protein 2 (NLRP2) and NLRP3 inflammasomes, and the activation of inflammasomes induces pyroptosis. Ghrelin, a gastrointestinal peptide, plays vital role in regulating inflammation and alleviating stress. Therefore, we proposed a hypothesis that ghrelin inhibits the activation of inflammasomes on astrocytes, reduces pyroptosis, and consequently prevents depression. We used lipopolysaccharide (LPS)-induced mouse depression model and cultured primary astrocytes in vitro to explore the mechanism of the antidepressant effect of ghrelin. Our results showed that ghrelin effectively inhibited acute inflammatory responses and damage in the hippocampus and prefrontal cortex. The activation of NLRP2 and NLRP3 in astrocytes induced by LPS was significantly inhibited by ghrelin. Pretreatment with ghrelin effectively suppressed LPS-induced upregulation of pyroptosis-related proteins and mRNA. Ghrelin alleviated cell membrane pore formation and cell swelling, ultimately improved LPS-induced depression-like behavior. In vitro, ghrelin prevented the LPS-induced upregulation of pyroptosis-related proteins and mRNA expression in astrocytes, and inhibited the initiation and assembly of NLRP2 and NLRP3. Ghrelin exhibits antidepressant effects, inhibits inflammasomes activation in astrocytes, and prevents pyroptosis, suggesting a novel strategy for treating depression. This groundbreaking study reveals new avenues for targeting potential therapeutic interventions to alleviate depression.
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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.