Role of IGF-1 in Neuroinflammation and Cogniton Deficits Induced by Sleep Deprivation

Abstract Background: Sleep deprivation negatively influences cognition, although inflammatory and immune responses participate in sleep deprivation,the molecular regulators of neuroinflammation after sleep deprivation remain to be defined. IGF-1 have shown anti-inflammatory and neuroprotective properties in models of CNS injury. This study investigated the role of IGF-1 on neuroinflammation and cognition deficits after sleep deprivation.Methods: Human periphery blood were obtained from chronic insomia(CI) patients to evaluated the levels of IGF-1. Mouse model of modified multiple platforms method (MMPM) was used to examine the role of IGF-1 in sleep deprivation. Behavior was evaluated by water maze tests.Inflammatory markers, and neuroinflammation were assessed by western blot and quantitative real-time PCR.Results: We found down-regulation of IGF-1 in human peripheral blood and in mice subjected to sleep deprivation for 5 days, and reduced activation of downstream the PI3K/AKT/GSK-3β pathway in mice brain. In conjunction, we found reduced levels of anti-apoptosis enzyme Bcl-2 and increased levels of pro-apoptosis enzyme Caspase-9, together with increased pro-inflammatory factors. Administration of IGF-1 induced activation of the PI3K/AKT/GSK-3β pathway, reversed changes in Bcl-2, Caspase-9 and pro-inflammatory factors, and prevented cognitive decline.Conclusion: These findings indicate that the IGF-1 reduces neuroinflammation and cogniton deficits after sleep deprivation. The effects may be mediated by the interaction among IGF-1 and PI3K/AKT/GSK-3β signaling. IGF-1 may be a viable therapeutic target that requires further investigations in sleep deprivation.