Activation of the Hippocampal DRD2 Alleviates Neuroinflammation, Synaptic Plasticity Damage and Cognitive Impairment After Sleep Deprivation

Sleep loss is commonplace nowadays and profoundly impacts cognition. Dopamine receptor D2 (DRD2) makes a specific contribution to cognition, although the precise mechanism underlying how DRD2 affects the cognitive process after sleep deprivation remains unclear. Herein, we observed cognitive impairment and impaired synaptic plasticity, including downregulation of synaptophysin and PSD95, decreased postsynaptic density thickness, neuron complexity, and spine density in chronic sleep restriction (CSR) mice. We also observed downregulated hippocampal DRD2 and Cryab expression in the CSR mice. Meanwhile, NF-& kappa;B translocation from the cytoplasm to the nucleus occurred, indicating that neuroinflammation ensued. However, hippocampal delivery of the DRD2 agonist quinpirole effectively rescued these changes. In vitro, quinpirole treatment significantly decreased the release of proinflammatory cytokines in microglial supernatant, indicating a potential anti-neuroinflammatory effect of Drd2/Cryab/NF-& kappa;B in CSR mice. Our study provided the evidence that activation of the Drd2 may relieve neuroinflammation and improve sleep deprivation-induced cognitive deficits.

Automated summary

Sleep loss has become common in modern society and has a significant impact on cognitive abilities. Activation of the dopamine receptor D2 (DRD2) has been found to play a specific role in cognition, but the exact mechanism of how DRD2 affects cognition after sleep deprivation is still unclear. This study observed cognitive impairment and impaired synaptic plasticity in mice with chronic sleep restriction (CSR), including downregulation of synaptophysin and PSD95, decreased postsynaptic density thickness, neuron complexity, and spine density. The study also found downregulation of hippocampal DRD2 and Cryab expression in CSR mice, as well as neuroinflammation indicated by NF-κB translocation. However, treatment with the DRD2 agonist quinpirole effectively reversed these changes, both in vitro and in vivo, suggesting a potential anti-neuroinflammatory effect of Drd2/Cryab/NF-κB in CSR mice.