Analysis of the Impact of CD200 on Neurodegenerative Diseases

Miller, Anne-Marie; Deighan, Brian F.; Downer, Eric J.; Lyons, Alan M.; Henrich‐Noack, Petra; Nolan, Yvonne M.

doi:10.5772/32003

Cited by 5 publications

(3 citation statements)

References 99 publications

(102 reference statements)

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“…Sung et al [ 70 ] also reported a decrease in the protein expression of CD200 and CD200R1 in the ventral midbrain in the chronic MPTP mouse model, 4 weeks after the last MPTP administration. A long-lasting decrease in CD200R1 and/or CD200 protein expression in the midbrain has also been reported in other in vivo experimental models of PD, such as the LPS model and the adenovirus-induced overexpression of human α-synuclein in SNpc [ 79 ] and the 6-OHDA rat model [ 56 ]. However, we observed that the mRNA levels of CD200full, CD200tr and CD200R1 returned to basal levels 7 days after MPTP administration, with the exception of CD200full RNA in the ventral midbrain.…”

Section: Discussionmentioning

confidence: 72%

The CD200R1 microglial inhibitory receptor as a therapeutic target in the MPTP model of Parkinson’s disease

Rabaneda-Lombarte

Serratosa

Bové

et al. 2021

J Neuroinflammation

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Background It is suggested that neuroinflammation, in which activated microglial cells play a relevant role, contributes to the development of Parkinson’s disease (PD). Consequently, the modulation of microglial activation is a potential therapeutic target to be taken into account to act against the dopaminergic neurodegeneration occurring in this neurological disorder. Several soluble and membrane-associated inhibitory mechanisms contribute to maintaining microglial cells in a quiescent/surveillant phenotype in physiological conditions. However, the presence of activated microglial cells in the brain in PD patients suggests that these mechanisms have been somehow overloaded. We focused our interest on one of the membrane-associated mechanisms, the CD200-CD200R1 ligand-receptor pair. Methods The acute MPTP experimental mouse model of PD was used to study the temporal pattern of mRNA expression of CD200 and CD200R1 in the context of MPTP-induced dopaminergic neurodegeneration and neuroinflammation. Dopaminergic damage was assessed by tyrosine hydroxylase (TH) immunoreactivity, and neuroinflammation was evaluated by the mRNA expression of inflammatory markers and IBA1 and GFAP immunohistochemistry. The effect of the modulation of the CD200-CD200R1 system on MPTP-induced damage was determined by using a CD200R1 agonist or CD200 KO mice. Results MPTP administration resulted in a progressive decrease in TH-positive fibres in the striatum and TH-positive neurons in the substantia nigra pars compacta, which were accompanied by transient astrogliosis, microgliosis and expression of pro- and anti-inflammatory markers. CD200 mRNA levels rapidly decreased in the ventral midbrain after MPTP treatment, while a transient decrease of CD200R1 mRNA expression was repeatedly observed in this brain area at earlier and later phases. By contrast, a transient increase in CD200R1 expression was observed in striatum. The administration of a CD200R1 agonist resulted in the inhibition of MPTP-induced dopaminergic neurodegeneration, while microglial cells showed signs of earlier activation in CD200-deficient mice. Conclusions Collectively, these findings provide evidence for a correlation between CD200-CD200R1 alterations, glial activation and neuronal loss. CD200R1 stimulation reduces MPTP-induced loss of dopaminergic neurons, and CD200 deficiency results in earlier microglial activation, suggesting that the potentiation of CD200R1 signalling is a possible approach to controlling neuroinflammation and neuronal death in PD.

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Section: Discussionmentioning

confidence: 72%

The CD200R1 microglial inhibitory receptor as a therapeutic target in the MPTP model of Parkinson’s disease

Rabaneda-Lombarte

Serratosa

Bové

et al. 2021

J Neuroinflammation

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“…Whether a similar mechanism contributes to BBB permeability remains to be assessed. However the CD200-CD200R interaction between endothelial cells and microglia (Miller et al, 2011), like neurons and astrocytes, increases production of inflammatory cytokines including IL-1b from microglia (Cox et al, 2013;Lyons et al, 2007a) creating an inflammatory microenvironment which has been shown to increase BBB permeability (Argaw et al, 2006;McCandless et al, 2009;Zhao et al, 2007). Similarly the age-related increase in neuroinflammatory changes, which have previously been coupled with increased IFNc expression (Lyons et al, 2011) and decreased CD200 expression (Lyons et al, 2007a), are associated with increased gadolinium extravasation and infiltration of macrophages (Blau et al, 2012), while recent findings have revealed similar age-related changes in APP/PS1 mice (Minogue et al, unpublished).…”

Section: Discussionmentioning

confidence: 99%

Classical activation of microglia in CD200-deficient mice is a consequence of blood brain barrier permeability and infiltration of peripheral cells

Denieffe

Kelly

McDonald

et al. 2013

Brain, Behavior, and Immunity

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The interaction between CD200, expressed on several cell types, and its receptor CD200R, expressed on cells of the myeloid lineage, has been shown to be an important factor in modulating inflammation in macrophage function in several conditions including colitis and arthritis. More recently its modulatory effect on microglial activation has been identified and CD200-deficiency has been associated with increased microglial activation accompanied by increased production of inflammatory cytokines. The response of glia prepared from CD200-deficient mice to stimuli like lipopolysaccharide (LPS) is markedly greater than the response of cells prepared from wildtype mice and, consistent with this, is the recent observation that expression of Toll-like receptor (TLR)4 and signalling through NFκB are increased in microglia prepared from CD200-deficient mice. Here we show that glia from CD200-deficient mice are also more responsive to interferon-γ (IFNγ) which triggers classical activation of microglia. We investigated the effects of CD200-deficiency in vivo and report that there is an increase in expression of several markers of microglial activation including tumor necrosis factor (TNF)-α, which is a hallmark of classically-activated microglia. These changes are accompanied by increased IFNγ, and the evidence suggests that this is produced by infiltrating cells including T cells and macrophages. We propose that these cells enter the brain as a consequence of increased blood brain barrier (BBB) permeability in CD200-deficient mice and that infiltration is assisted by increased expression of the chemokines, monocyte chemotactic protein-1 (MCP-1), IFNγ-induced protein-10 (IP-10) and RANTES. This may have implications in neurodegenerative diseases where BBB permeability is compromised.

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“…Therefore, there is a direct neuronal mechanism for regulating microglial activity, and loss of this interaction during neuronal cell degeneration may stimulate up-regulation of CD200, facilitating microglial activation. We and others have provided recent evidence to implicate the impairment of CD200-CD200R interaction as a contributing factor in PD neurodegeneration (Bieschke et al, 2011;Miller et al, 2011). Blockade of CD200R was shown to selectively and significantly enhance dopaminergic neuronal cell susceptibility to rotenone and iron-induced neurotoxicity in mesencephalic neuron-glia co-cultures.…”

Section: Neuroinflammation In Parkinson's Diseasementioning

confidence: 99%

Contributions of central and systemic inflammation to the pathophysiology of Parkinson's disease

Collins¹,

Toulouse²,

Connor³

et al. 2012

Neuropharmacology

249

151

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Analysis of the Impact of CD200 on Neurodegenerative Diseases

Cited by 5 publications

References 99 publications

The CD200R1 microglial inhibitory receptor as a therapeutic target in the MPTP model of Parkinson’s disease

The CD200R1 microglial inhibitory receptor as a therapeutic target in the MPTP model of Parkinson’s disease

Classical activation of microglia in CD200-deficient mice is a consequence of blood brain barrier permeability and infiltration of peripheral cells

Contributions of central and systemic inflammation to the pathophysiology of Parkinson's disease

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