Department of Anaesthesiology & Center for Brain Science, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710061, China.
Department of Anaesthesiology, Yan'an University Affiliated Hospital, Yan'an, 716000, China.
Mol Neurobiol. 2023 Dec;60(12):7208-7221. doi: 10.1007/s12035-023-03514-5. Epub 2023 Aug 5.
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-κB 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-κB in CSR mice. Our study provided the evidence that activation of the Drd2 may relieve neuroinflammation and improve sleep deprivation-induced cognitive deficits.
如今，睡眠不足是很常见的，它会深刻影响认知。多巴胺受体 D2（DRD2）对认知有特定的贡献，尽管 DRD2 影响睡眠剥夺后认知过程的确切机制尚不清楚。在此，我们观察到慢性睡眠限制（CSR）小鼠出现认知障碍和突触可塑性受损，包括突触小体素和 PSD95 下调、突触后密度厚度、神经元复杂性和棘密度降低，在 CSR 小鼠中还观察到海马体 DRD2 和 Cryab 表达下调。同时，NF-κB 从细胞质向细胞核易位，表明随后发生神经炎症。然而，海马体给予 DRD2 激动剂喹吡罗可有效挽救这些变化。在体外，喹吡罗处理可显著减少小胶质细胞上清液中促炎细胞因子的释放，表明 Drd2/Cryab/NF-κB 在 CSR 小鼠中具有潜在的抗神经炎症作用。我们的研究提供了证据，表明激活 Drd2 可能缓解神经炎症并改善睡眠剥夺引起的认知缺陷。
