CD200-CD200R dysfunction exacerbates microglial activation and dopaminergic neurodegeneration in a rat model of Parkinson's disease
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BACKGROUND: Increasing evidence suggests that microglial activation may participate in the aetiology and pathogenesis of Parkinson's disease (PD). CD200-CD200R signalling has been shown to be critical for restraining microglial activation. We have previously shown that expression of CD200R in monocyte-derived macrophages, induced by various stimuli, is impaired in PD patients, implying an intrinsic abnormality of CD200-CD200R signalling in PD brain. Thus, further in vivo evidence is needed to elucidate the role of malfunction of CD200-CD200R signalling in the pathogenesis of PD. METHODS: 6-hydroxydopamine (6-OHDA)-lesioned rats were used as an animal model of PD. CD200R-blocking antibody (BAb) was injected into striatum to block the engagement of CD200 and CD200R. The animals were divided into three groups, which were treated with 6-OHDA/Veh (PBS), 6-OHDA/CAb (isotype control antibody) or 6-OHDA/BAb, respectively. Rotational tests and immunohistochemistry were employed to evaluate motor deficits and dopaminergic neurodegeneration in animals from each group. HPLC analysis was used to measure monoamine levels in striatum. Morphological analysis and quantification of CD11b- (or MHC II-) immunoreactive cells were performed to investigate microglial activation and possible neuroinflammation in the substantia nigra (SN). Finally, ELISA was employed to assay protein levels of proinflammatory cytokines. RESULTS: Compared with 6-OHDA/CAb or 6-OHDA/Veh groups, rats treated with 6-OHDA/BAb showed a significant increase in counts of contralateral rotation and a significant decrease in TH-immunoreactive (TH-ir) neurons in SN. A marked decrease in monoamine levels was also detected in 6-OHDA/BAb-treated rats, in comparison to 6-OHDA/Veh-treated ones. Furthermore, remarkably increased activation of microglia as well as up-regulation of proinflammatory cytokines was found concomitant with dopaminergic neurodegeneration in 6-OHDA/BAb-treated rats. CONCLUSIONS: This study shows that deficits in the CD200-CD200R system exacerbate microglial activation and dopaminergic neurodegeneration in a 6-OHDA-induced rat model of PD. Our results suggest that dysfunction of CD200-CD200R signalling may be involved in the aetiopathogenesis of PD.
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In rat PD models, deficiency of CX3CL1 or CX3CR1 and dysfunction of CD200-CD200R signaling increase microglial activation and degeneration of DA neurons.
“In rat PD models, both deficiency CX3CL1 or CX3CR1 as well as the dysfunction of CD200-CD200R signaling have been shown to increase microglial activation and the degeneration of DA neurons (Wang et al., 2011; Zhang et al., 2011).”
From The role of microglia in retinal neurodegeneration: Alzheimer’s disease, parkinson, and glaucoma. (2017) · cites this paper as Zhang et al., 2011
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- Authors
- Zhang, S., Wang, X.-J., Tian, L.-P., Pan, J., Lu, G.-Q., Zhang, Y.-J., Ding, J.-Q., & Chen, S.-D.
- Affiliations
- Shanghai Jiao Tong University (CN)
- ORCID
- Pan, Jing
- Venue
- Journal of Neuroinflammation
- Published
- 2011-11-06
- Volume
- 8
- Issue
- 1
- Pages
- 154-154
- ISSN
- 1742-2094 (ISSN-L)
- PMC
- PMC3226566
- OpenAlex
- W2033271712
- Cited by
- 154
- References
- 85
- Citations by year
- 2026: 3 · 2025: 7 · 2024: 13 · 2023: 12 · 2022: 8 · 2021: 11 · 2020: 10 · 2019: 13 · 2018: 10 · 2017: 8 · 2016: 10 · 2015: 8 · 2014: 16 · 2013: 16 · 2012: 8
- FWCI
- 7.24
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by
- Locations
- Journal of Neuroinflammation (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- 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, microglial activation, dopaminergic neuron loss, 6-hydroxydopamine lesion, substantia nigra, neuroinflammation, inflammatory cytokines, monoamine levels, motor impairment, striatum, neuroprotection, rat model
- MeSH terms
- Animals, Behavior, Animal, Disease Models, Animal, Dopamine, Humans, Male, Nerve Degeneration, Receptors, Immunologic, Antigens, CD, Oxidopamine, Rats, Sprague-Dawley, Microglia, Antibodies, Blocking, Parkinsonian Disorders, Rats, Dopaminergic Neurons
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