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Nr1d1 Mediates Microglial Inflammatory Activation Induced by Intermittent Hypoxia: A Transcriptomic and Machine
Zhuoran Sun1,2, Tengqun Shen1, Mengfan Li1
1Department of Neurology, Weihai Municipal Hospital, Shandong University, Jinan, Shandong, China.
Journal of Molecular Neuroscience : MN
|July 11, 2026
Summary
Obstructive sleep apnea causes intermittent hypoxia, leading to brain inflammation. This study identifies Nr1d1 as a key gene involved in microglial activation during this process.
Area of Science:
- Neuroscience
- Immunology
- Genetics
Background:
- Obstructive sleep apnea (OSA) involves recurrent intermittent hypoxia (IH), a known contributor to neuroinflammation and neurological deficits.
- Microglia, the brain's immune cells, play a crucial role in inflammatory responses, but the specific molecular pathways activated by IH are not fully understood.
Purpose of the Study:
- To identify key genes mediating microglial activation under IH conditions.
- To investigate the functional significance of these genes in IH-induced neuroinflammation.
Main Methods:
- An in vitro model of IH was established using BV2 microglial cells.
- Inflammation markers (COX2, iNOS, IL-6, TNF-α) were measured using Western blot and ELISA.
- RNA sequencing was employed to analyze transcriptional changes.
- Bioinformatic analyses including differential expression, enrichment, network, and machine learning were performed.
- Pharmacological inhibition of candidate gene Nr1d1 was used to assess its role.
Main Results:
- IH significantly elevated inflammatory markers (COX2, iNOS, IL-6, TNF-α) in BV2 cells.
- Transcriptomic profiling revealed distinct gene expression patterns between control and IH conditions.
- Network analysis identified a cluster of circadian genes, including Nr1d1, as central to IH-responsive transcriptional changes.
- Inhibition of Nr1d1 demonstrably reduced IH-induced inflammatory responses in microglial cells.
Conclusions:
- Intermittent hypoxia triggers significant inflammatory activation and transcriptional reprogramming in microglial cells.
- Nr1d1 emerges as a potential key regulator, linking circadian rhythms to microglial inflammatory activation in the context of IH.
- Targeting Nr1d1 may offer a therapeutic strategy for mitigating neuroinflammation associated with obstructive sleep apnea.
