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

Abstract

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.

• Authors: Hui Gao, Yuxin Zhang, Danlei Luo, Jing Xu, Shuwen Tan, Ying Li, Wanling Qi, Qian Zhai, Qiang Wang
• Journal: Molecular neurobiology (Mol Neurobiol) Vol. 60 Issue 12 Pg. 7208-7221 (Dec 2023) ISSN: 1559-1182 [Electronic] United States
• PMID: 37543530 (Publication Type: Journal Article)
• Copyright: © 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.

Chemical References

• NF-kappa B
• Quinpirole
• DRD2 protein, mouse
• Receptors, Dopamine D2

Topics

• Animals
• Mice
• Sleep Deprivation (complications)
• NF-kappa B
• Neuroinflammatory Diseases
• Quinpirole
• Cognitive Dysfunction (drug therapy)
• Hippocampus
• Neuronal Plasticity
• Receptors, Dopamine D2