Chronic neuroinflammation is common in aging and neurodegenerative disorders. However, the molecular and cellular mechanisms have not been completely elucidated. In this study the authors find that dopamine D2 receptors in brain astrocytes inhibit neuroinflammation via αB-crystallin. Knockout mice lacking D2 receptors show enhanced inflammatory response in multiple central nervous system regions and increased vulnerability of nigral dopaminergic neurons to the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Treatment of wild-type mice with the selective D2 receptor agonist quinpirole increased resistance of nigral dopaminergic neurons to MPTP through partial suppression of inflammation. The authors concluded that astrocytic D2 receptor activation normally suppresses neuroinflammation in the central nervous system through an αB-crystallin -dependent mechanism. Development of new drugs targeting astrocyte-mediated innate immune response in the central nervous system may be useful for disorders of aging and neurodegenerative disease.
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, Zhou JW: Suppression of neuroinflammation by astrocytic dopamine D2 receptors via αB-crystallin. Nature [Epub ahead of print, Dec 16 (2012); doi: 10.1038/nature11748].