Cited by 108Neuroinflammation and Neurodegeneration MechanismsParkinson's Disease Mechanisms and TreatmentsNuclear Receptors and Signaling

Impaired CD200-CD200R-mediated microglia silencing enhances midbrain dopaminergic neurodegeneration: roles of aging, superoxide, NADPH oxidase, and p38 MAPK

Wang, Xi-Jin, Zhang, Shi, Yan, Zhi-Qiang, Zhao, Yan-Xin, Zhou, Hai-Yan, Wang, Ying, Lu, Guo-Qiang, Zhang, Jing-Dong·2011·Free Radical Biology and Medicine

Abstract

CD200-CD200R signaling holds microglia in a quiescent state. Parkinson disease (PD) neurodegeneration may be associated with impairment of CD200-CD200R-mediated microglia silencing in the substantia nigra (SN). In this study, an anti-CD200R blocking antibody (ACDR) selectively and significantly enhanced the susceptibility of dopaminergic neurons to neurotoxicity induced by rotenone (Rot) and iron (Ir) in mesencephalic neuron/glia cultures. Microglia were shown to mediate dopaminergic neurotoxicity induced by ACDR/Rot (combination of ACDR and Rot) and ACDR/Ir (combination of ACDR and Ir). ACDR significantly enhanced the microglial activation induced by Rot and Ir in neuron/glia cultures. NADPH oxidase-mediated superoxide generation was a key contributor to dopaminergic neurotoxicity induced by ACDR/Rot and ACDR/Ir. p38 MAPK contributed to NADPH oxidase activation induced by ACDR/Rot and ACDR/Ir. Interestingly, there were a decrease in CD200 expression (mRNA and protein) and an enhancement of microglial response (MHCII mRNA and ICAM-1 protein) in the rat SN with aging. ICAM-1 expression was significantly inversely correlated with CD200 expression. These results strongly indicate the participation of SN CD200-CD200R dysfunction in the etiopathogenesis of PD and provide a new insight into the molecular mechanisms underlying the involvement of aging in PD and help to elucidate the mechanisms of the combined involvement of immune/inflammatory factors, environmental substances, and aging in PD.

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Crossref · 10.1016/j.freeradbiomed.2011.01.032

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Authors
Wang, X.-J., Zhang, S., Yan, Z.-Q., Zhao, Y.-X., Zhou, H.-Y., Wang, Y., Lu, G.-Q., & Zhang, J.-D.
Affiliations
  • Chinese Academy of Sciences (CN)
  • Shanghai Jiao Tong University (CN)
  • University of Nebraska Medical Center (US)
Venue
Free Radical Biology and Medicine
Publisher
Elsevier BV
Published
2011-05
Volume
50
Issue
9
Pages
1094-1106
ISSN
0891-5849 (ISSN-L)
OpenAlex
W2078755005
Cited by
108
References
62
Citations by year
2026: 4 · 2025: 3 · 2024: 4 · 2023: 2 · 2022: 8 · 2021: 6 · 2020: 16 · 2019: 6 · 2018: 8 · 2017: 7 · 2016: 6 · 2015: 7 · 2014: 10 · 2013: 5 · 2012: 11
FWCI
5.48
Type
journal article
Language
en
Open access
closed
Locations
  • Free Radical Biology and Medicine (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
  • Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Nuclear Receptors and Signaling
Keywords
Parkinson's disease, dopaminergic neuron loss, substantia nigra, rotenone, iron neurotoxicity, NADPH oxidase, superoxide, p38 MAPK, aging, ICAM-1, MHC class II, microglial activation
MeSH terms
Aging, Animals, Cells, Cultured, Dopamine, Iron, Mesencephalon, Neurons, Parkinson Disease, Receptors, Immunologic, Rotenone, Superoxides, Antigens, CD, Gene Expression, Polymerase Chain Reaction, Rats, Sprague-Dawley, Microglia, Intercellular Adhesion Molecule-1, Cell Culture Techniques, Antibodies, Blocking, NADPH Oxidases, p38 Mitogen-Activated Protein Kinases, Rats

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