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Review
. 2020 Sep;68(9):1874-1890.
doi: 10.1002/glia.23811. Epub 2020 Feb 29.

CD200 maintains the region-specific phenotype of microglia in the midbrain and its role in Parkinson's disease

Le Wang  1 , Xiaoli Gong  2 , Yang Liu  1 , Tianshu Du  1 , Zhen Zhang  1 , Ting Zhang  1 , Xiaomin Wang  1
Affiliations
Review

CD200 maintains the region-specific phenotype of microglia in the midbrain and its role in Parkinson's disease

Le Wang et al. Glia. 2020 Sep.

Abstract

Microglia are a specialized population of tissue macrophages in the mammalian brain. Microglial phenotype is tightly regulated by local environmental factors, although little is known about these factors and their region-preferred roles in regulating local neuroinflammatory responses. We hypothesized that microglia in different brain regions respond differently to neuroinflammatory stimulation and that CD200, an anti-inflammatory protein mainly originated from neurons, acts as a local cue inhibiting microglia activation in the midbrain. We utilized a CD200-deficient mouse line to analyze the phenotypic role of CD200 in the regulation of normal neuron-microglia homeostasis in the midbrain and in the dopaminergic degeneration in an α-synuclein overexpression model of PD. We found that systemic administration of an endotoxin lipopolysaccharide induced a region-preferred change in CD200 expression in the midbrain. Similarly, CD200-/- mice showed a regional preference in an enhancement of microglia activation and baseline inflammatory levels in the midbrain and dopamine neuron loss in the substantia nigra (SN). In a mouse model of Parkinson's disease (PD) induced by rAAV-hSYN injection into the SN, CD200-/- mice showed more dopamine neuron loss in the SN than wild type mice. Activation of CD200 receptors with a CD200 fusion protein alleviated the neuroinflammation and neuronal death in the SN of PD mice. These findings demonstrate that CD200 is essential for the midbrain homeostasis and acts as a critical local regulator in controlling microglial properties related to the PD pathogenesis.

Keywords: CD200; Parkinson's disease; microglia.

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