PMID:23242137

Citation	Shao, W, Zhang, SZ, Tang, M, Zhang, XH, Zhou, Z, Yin, YQ, Zhou, QB, Huang, YY, Liu, YJ, Wawrousek, E, Chen, T, Li, SB, Xu, M, Zhou, JN, Hu, G and Zhou, JW (2013) Suppression of neuroinflammation by astrocytic dopamine D2 receptors via αB-crystallin. Nature 494:90-4
Abstract	Chronic neuroinflammation is a common feature of the ageing brain and some neurodegenerative disorders. However, the molecular and cellular mechanisms underlying the regulation of innate immunity in the central nervous system remain elusive. Here we show that the astrocytic dopamine D2 receptor (DRD2) modulates innate immunity through αB-crystallin (CRYAB), which is known to suppress neuroinflammation. We demonstrate that knockout mice lacking Drd2 showed remarkable inflammatory response in multiple central nervous system regions and increased the vulnerability of nigral dopaminergic neurons to neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced neurotoxicity. Astrocytes null for Drd2 became hyper-responsive to immune stimuli with a marked reduction in the level of CRYAB. Preferential ablation of Drd2 in astrocytes robustly activated astrocytes in the substantia nigra. Gain- or loss-of-function studies showed that CRYAB is critical for DRD2-mediated modulation of innate immune response in astrocytes. Furthermore, treatment of wild-type mice with the selective DRD2 agonist quinpirole increased resistance of the nigral dopaminergic neurons to MPTP through partial suppression of inflammation. Our study indicates that astrocytic DRD2 activation normally suppresses neuroinflammation in the central nervous system through a CRYAB-dependent mechanism, and provides a new strategy for targeting the astrocyte-mediated innate immune response in the central nervous system during ageing and disease.
Links	PubMed Online version:10.1038/nature11748
Keywords
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Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
MOUSE:DRD2		GO:0045824: negative regulation of innate immune response	ECO:0000315:		P		Figure 2 in this publication displays data that the authors found to indicate that Drd2 knockout mice were hyper-responsive with higher neuroinflammation	complete CACAO 6437
MOUSE:DRD2	involved_in	GO:0045824: negative regulation of innate immune response	ECO:0000315: mutant phenotype evidence used in manual assertion		P		Seeded From UniProt	complete

References

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