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Wild-type microglia arrest pathology in a mouse model of Rett syndrome

Overview of attention for article published in Nature, March 2012
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  • In the top 5% of all research outputs scored by Altmetric
  • High Attention Score compared to outputs of the same age (99th percentile)
  • High Attention Score compared to outputs of the same age and source (82nd percentile)

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Title
Wild-type microglia arrest pathology in a mouse model of Rett syndrome
Published in
Nature, March 2012
DOI 10.1038/nature10907
Pubmed ID
Authors

Noël C. Derecki, James C. Cronk, Zhenjie Lu, Eric Xu, Stephen B. G. Abbott, Patrice G. Guyenet, Jonathan Kipnis

Abstract

Rett syndrome is an X-linked autism spectrum disorder. The disease is characterized in most cases by mutation of the MECP2 gene, which encodes a methyl-CpG-binding protein. Although MECP2 is expressed in many tissues, the disease is generally attributed to a primary neuronal dysfunction. However, as shown recently, glia, specifically astrocytes, also contribute to Rett pathophysiology. Here we examine the role of another form of glia, microglia, in a murine model of Rett syndrome. Transplantation of wild-type bone marrow into irradiation-conditioned Mecp2-null hosts resulted in engraftment of brain parenchyma by bone-marrow-derived myeloid cells of microglial phenotype, and arrest of disease development. However, when cranial irradiation was blocked by lead shield, and microglial engraftment was prevented, disease was not arrested. Similarly, targeted expression of MECP2 in myeloid cells, driven by Lysm(cre) on an Mecp2-null background, markedly attenuated disease symptoms. Thus, through multiple approaches, wild-type Mecp2-expressing microglia within the context of an Mecp2-null male mouse arrested numerous facets of disease pathology: lifespan was increased, breathing patterns were normalized, apnoeas were reduced, body weight was increased to near that of wild type, and locomotor activity was improved. Mecp2(+/-) females also showed significant improvements as a result of wild-type microglial engraftment. These benefits mediated by wild-type microglia, however, were diminished when phagocytic activity was inhibited pharmacologically by using annexin V to block phosphatydilserine residues on apoptotic targets, thus preventing recognition and engulfment by tissue-resident phagocytes. These results suggest the importance of microglial phagocytic activity in Rett syndrome. Our data implicate microglia as major players in the pathophysiology of this devastating disorder, and suggest that bone marrow transplantation might offer a feasible therapeutic approach for it.

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Mendeley readers

Mendeley readers

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Geographical breakdown

Country Count As %
United States 18 3%
United Kingdom 5 <1%
Germany 3 <1%
China 3 <1%
France 2 <1%
Netherlands 2 <1%
Japan 2 <1%
Chile 2 <1%
Argentina 1 <1%
Other 6 <1%
Unknown 674 94%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 182 25%
Researcher 159 22%
Student > Bachelor 70 10%
Student > Master 52 7%
Professor > Associate Professor 38 5%
Other 127 18%
Unknown 90 13%
Readers by discipline Count As %
Agricultural and Biological Sciences 281 39%
Neuroscience 138 19%
Medicine and Dentistry 74 10%
Biochemistry, Genetics and Molecular Biology 51 7%
Immunology and Microbiology 15 2%
Other 55 8%
Unknown 104 14%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 107. 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 20 June 2023.
All research outputs
#390,584
of 25,392,205 outputs
Outputs from Nature
#19,438
of 97,650 outputs
Outputs of similar age
#1,687
of 169,757 outputs
Outputs of similar age from Nature
#179
of 1,044 outputs
Altmetric has tracked 25,392,205 research outputs across all sources so far. Compared to these this one has done particularly well and is in the 98th percentile: it's in the top 5% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 97,650 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 102.3. This one has done well, scoring higher than 80% of its peers.
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 169,757 tracked outputs that were published within six weeks on either side of this one in any source. This one has done particularly well, scoring higher than 99% of its contemporaries.
We're also able to compare this research output to 1,044 others from the same source and published within six weeks on either side of this one. This one has done well, scoring higher than 82% of its contemporaries.