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Purinergic receptors P2Y12R and P2X7R: potential targets for PET imaging of microglia phenotypes in multiple sclerosis

Overview of attention for article published in Journal of Neuroinflammation, December 2017
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Title
Purinergic receptors P2Y12R and P2X7R: potential targets for PET imaging of microglia phenotypes in multiple sclerosis
Published in
Journal of Neuroinflammation, December 2017
DOI 10.1186/s12974-017-1034-z
Pubmed ID
Authors

Wissam Beaino, Bieneke Janssen, Gijs Kooij, Susanne M. A. van der Pol, B. van Het Hof, Jack van Horssen, Albert D. Windhorst, Helga E. de Vries

Abstract

Microglia are major players in the pathogenesis of multiple sclerosis (MS) and may play a dual role in disease progression. The activation status of microglia in vivo is highly dynamic and occurs as a continuum, with the pro-inflammatory and anti-inflammatory phenotypes on either end of this spectrum. Little is known about in vivo dynamics of microglia phenotypes in MS due to the lack of diagnostic tools. Positron emission tomography (PET) imaging is a powerful non-invasive technique that allows real-time imaging of microglia activation phenotypes in the central nervous system, depending on the availability of selective PET tracers. Our objective is to investigate and characterize the expression of the purinergic receptors P2Y12R and P2X7R as potential targets for PET tracer development and subsequent PET imaging in order to evaluate the dynamics of microglia status in vivo. We used immunohistochemical analysis to explore the expression of P2Y12R and P2X7R in experimental autoimmune encephalomyelitis (EAE) post-mortem tissues and different stages of well-characterized MS lesions. We evaluated by quantitative real-time polymerase chain reaction the expression of P2Y12R and P2X7R in human polarized microglia, and we performed autoradiography binding assay with radiolabeled P2Y12R and P2X7R antagonists using MS and rat EAE tissues. Here, we demonstrate that P2X7R is associated with a pro-inflammatory phenotype of human microglia in vitro, and is highly expressed in microglia in MS lesions as well as during the peak of EAE. In contrast, P2Y12R was associated with an anti-inflammatory phenotype in human microglia in vitro and was expressed at lower levels in active inflammatory MS lesions compared to normal-appearing white matter (NAWM) and similarly in EAE, while its expression increased in the remission phase of EAE. Binding of radiolabeled tracers specific for P2Y12R and P2X7R on ex vivo tissues validated the value of these receptors as PET imaging targets for microglia phenotypes in vivo. Our results suggest that P2Y12R and P2X7R are excellent targets for PET imaging to discriminate distinct microglia phenotypes in MS. Ultimately, this may provide insight into the role of microglia in disease progression and monitor novel treatment strategies to alter microglia phenotype.

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Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 108 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 108 100%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 21 19%
Researcher 21 19%
Student > Master 14 13%
Student > Bachelor 7 6%
Other 3 3%
Other 13 12%
Unknown 29 27%
Readers by discipline Count As %
Neuroscience 19 18%
Medicine and Dentistry 14 13%
Agricultural and Biological Sciences 8 7%
Chemistry 8 7%
Biochemistry, Genetics and Molecular Biology 6 6%
Other 18 17%
Unknown 35 32%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 25 December 2017.
All research outputs
#15,688,569
of 23,313,051 outputs
Outputs from Journal of Neuroinflammation
#1,788
of 2,692 outputs
Outputs of similar age
#270,159
of 442,496 outputs
Outputs of similar age from Journal of Neuroinflammation
#32
of 66 outputs
Altmetric has tracked 23,313,051 research outputs across all sources so far. This one is in the 22nd percentile – i.e., 22% of other outputs scored the same or lower than it.
So far Altmetric has tracked 2,692 research outputs from this source. They typically receive more attention than average, with a mean Attention Score of 7.6. This one is in the 26th percentile – i.e., 26% of its peers scored the same or lower than it.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 442,496 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 29th percentile – i.e., 29% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 66 others from the same source and published within six weeks on either side of this one. This one is in the 43rd percentile – i.e., 43% of its contemporaries scored the same or lower than it.