ArticleJournal of advanced research2025
Neopterin mediates sleep deprivation-induced microglial activation resulting in neuronal damage by affecting YY1/HDAC1/TOP1/IL-6 signaling.
Article in Journal of advanced research, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed.
- Article
- Association Between Sleep Debt and Mental Well-Being in School-Aged Children and Adolescents in China: A Multi-Province, Cross-Sectional, Observational Study.Healthcare (Basel, Switzerland) · 2026Article
- Transcriptional remodeling of human skeletal muscle following sleep restriction in postmenopausal women.Physiological genomics · 2026Article
- Alterations in the DTI-ALPS index and choroid plexus volume are associated with symptom severity in children with tic disorders.BMC neurology · 2026Article
- The Function of Microglia in Cognitive Impairment Influenced by Sleep Deprivation.Cellular and molecular neurobiology · 2026Review
- Neuroimaging evidence of mitochondrial dysfunction and inflammation in psychiatric disorders: a review.Psychoradiology · 2026Review
- Exploring the Mechanism of 2,4-Dichlorophenoxyacetic Acid in Causing Neurodegenerative Diseases Based on Network Toxicology and Molecular Docking.International journal of molecular sciences · 2025Article
- Topoisomerase IIα orchestrates secretion of IL-6 and IL-8 with human papillomavirus replication.Virologica Sinica · 2025Article
- COG1410 Alleviated Chronic Sleep Deprivation-Induced Memory Loss by Regulating Microglial Phagocytosis and Inhibiting Hippocampal Inflammation.ACS chemical neuroscience · 2025Article
- Age-Specific Functional Connectivity Changes After Partial Sleep Deprivation Are Correlated With Neurocognitive and Molecular Signatures.CNS neuroscience & therapeutics · 2025Article
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Authors and funding
5 authors.
Funding
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Abstract
introductionSleep deprivation (SD) is a common disorder in modern society. Hippocampus is an important region of the brain for learning, memory, and emotions. Dysfunction of hippocampus can lead to severe learning and memory disorder, significantly affecting quality of life. SD is accompanied by hippocampal microglia activation and a surge in inflammatory factors, but the precise mechanism remains unclear. Moreover, the ongoing unknown persists regarding how activated microglia in SD lead to neuronal damage. Topoisomerase 1 (TOP1) plays an essential role in the inflammatory process, including the tumor system and viral infection. In this study, we observed a significant elevation in TOP1 levels in the hippocampus of mice subjected to SD. Therefore, we hypothesize that TOP1 may be implicated in SD-induced microglia activation and neuronal damage.
objectivesTo investigate the role of TOP1 in SD-induced microglial activation, neuronal damage, and neurobehavioral impairments, and the molecular basis of SD-induced elevated TOP1 levels.
methodsTOP1-specific knockout mice in microglia were used to study the effects of TOP1 on microglial activation and neuronal damage. Transcription factor prediction, RNA interference, ChIP-qPCR, ChIP-seq database analysis, and luciferase reporter assays were performed to explore the molecular mechanisms of YY1 transcriptional activation. Untargeted metabolic profiling was employed to investigate the material basis of YY1 transcriptional activation.
resultsKnockdown of TOP1 in hippocampal microglia ameliorates SD-induced microglial activation, inflammatory response, and neuronal damage. Mechanistically, TOP1 mediates the release of IL-6 from microglia, which consequently leads to neuronal dysfunction. Moreover, elevated TOP1 due to SD were associated with neopterin, which was attributed to its promotion of elevated levels of H3K27ac in the TOP1 promoter region by disrupting the binding of YY1 and HDAC1.
conclusionThe present study reveals that TOP1-mediated microglial activation is critical for SD induced hippocampal neuronal damage and behavioral impairments.
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