Olfml3 Regulates Microglial Inflammation and Neuronal Injury in Obstructive Sleep Apnea via Cybb-Mediated TLR4/NF-κB...

Area of Science:

• Neuroscience
• Immunology
• Genetics

Background:

• Obstructive sleep apnea (OSA) is linked to neurocognitive impairment, primarily due to intermittent hypoxia (IH)-induced neuroinflammation.
• Microglia are key players in this IH-induced neuroinflammation, but the role of Olfml3 is not well understood.

Purpose of the Study:

• To investigate the role of Olfml3 in microglia during IH-induced neuroinflammation in OSA.
• To elucidate the molecular mechanisms by which Olfml3 affects microglial activation and neuronal injury.

Main Methods:

• Single-cell RNA sequencing (scRNA-seq) and in vitro/vivo OSA models were used.
• Assessed Olfml3 expression, microglial polarization, inflammatory cytokines, reactive oxygen species (ROS), and TLR4/NF-κB pathway activation.
• Evaluated cognitive function, brain pathology, and neuronal injury in mice.

Main Results:

• Olfml3 expression in microglia negatively correlated with Cybb.
• Olfml3 overexpression reduced microglial inflammation and neuronal injury by suppressing the Cybb/TLR4/NF-κB pathway.
• In vivo studies confirmed Olfml3's protective effect against IH-induced neuroinflammation in OSA.

Conclusions:

• Olfml3 in microglia mitigates IH-induced proinflammatory activation and neuronal injury.
• The protective mechanism involves the Cybb/TLR4/NF-κB axis.
• Olfml3 confers neuroprotection against OSA-associated neuroinflammation.