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Dendrimer-mediated delivery of N-acetyl cysteine to microglia in a mouse model of Rett syndrome

Overview of attention for article published in Journal of Neuroinflammation, December 2017
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  • Good Attention Score compared to outputs of the same age (69th percentile)
  • Good Attention Score compared to outputs of the same age and source (73rd percentile)

Mentioned by

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2 tweeters
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1 Wikipedia page

Citations

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44 Dimensions

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70 Mendeley
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Title
Dendrimer-mediated delivery of N-acetyl cysteine to microglia in a mouse model of Rett syndrome
Published in
Journal of Neuroinflammation, December 2017
DOI 10.1186/s12974-017-1004-5
Pubmed ID
Authors

Elizabeth Nance, Siva P. Kambhampati, Elizabeth S. Smith, Zhi Zhang, Fan Zhang, Sarabdeep Singh, Michael V. Johnston, Rangaramanujam M. Kannan, Mary E. Blue, Sujatha Kannan

Abstract

Rett syndrome (RTT) is a pervasive developmental disorder that is progressive and has no effective cure. Immune dysregulation, oxidative stress, and excess glutamate in the brain mediated by glial dysfunction have been implicated in the pathogenesis and worsening of symptoms of RTT. In this study, we investigated a new nanotherapeutic approach to target glia for attenuation of brain inflammation/injury both in vitro and in vivo using a Mecp2-null mouse model of Rett syndrome. To determine whether inflammation and immune dysregulation were potential targets for dendrimer-based therapeutics in RTT, we assessed the immune response of primary glial cells from Mecp2-null and wild-type (WT) mice to LPS. Using dendrimers that intrinsically target activated microglia and astrocytes, we studied N-acetyl cysteine (NAC) and dendrimer-conjugated N-acetyl cysteine (D-NAC) effects on inflammatory cytokines by PCR and multiplex assay in WT vs Mecp2-null glia. Since the cysteine-glutamate antiporter (Xc-) is upregulated in Mecp2-null glia when compared to WT, the role of Xc- in the uptake of NAC and L-cysteine into the cell was compared to that of D-NAC using BV2 cells in vitro. We then assessed the ability of D-NAC given systemically twice weekly to Mecp2-null mice to improve behavioral phenotype and lifespan. We demonstrated that the mixed glia derived from Mecp2-null mice have an exaggerated inflammatory and oxidative stress response to LPS stimulation when compared to WT glia. Expression of Xc- was significantly upregulated in the Mecp2-null glia when compared to WT and was further increased in the presence of LPS stimulation. Unlike NAC, D-NAC bypasses the Xc- for cell uptake, increasing intracellular GSH levels while preventing extracellular glutamate release and excitotoxicity. Systemically administered dendrimers were localized in microglia in Mecp2-null mice, but not in age-matched WT littermates. Treatment with D-NAC significantly improved behavioral outcomes in Mecp2-null mice, but not survival. These results suggest that delivery of drugs using dendrimer nanodevices offers a potential strategy for targeting glia and modulating oxidative stress and immune responses in RTT.

Twitter Demographics

The data shown below were collected from the profiles of 2 tweeters who shared this research output. Click here to find out more about how the information was compiled.

Mendeley readers

The data shown below were compiled from readership statistics for 70 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 70 100%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 15 21%
Researcher 10 14%
Student > Master 7 10%
Student > Bachelor 6 9%
Professor 4 6%
Other 11 16%
Unknown 17 24%
Readers by discipline Count As %
Neuroscience 11 16%
Agricultural and Biological Sciences 10 14%
Biochemistry, Genetics and Molecular Biology 9 13%
Medicine and Dentistry 6 9%
Chemical Engineering 3 4%
Other 14 20%
Unknown 17 24%

Attention Score in Context

This research output has an Altmetric Attention Score of 5. 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 30 April 2020.
All research outputs
#4,844,733
of 17,595,144 outputs
Outputs from Journal of Neuroinflammation
#864
of 2,151 outputs
Outputs of similar age
#127,363
of 416,949 outputs
Outputs of similar age from Journal of Neuroinflammation
#48
of 179 outputs
Altmetric has tracked 17,595,144 research outputs across all sources so far. This one has received more attention than most of these and is in the 72nd percentile.
So far Altmetric has tracked 2,151 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 6.8. This one has gotten more attention than average, scoring higher than 59% 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 416,949 tracked outputs that were published within six weeks on either side of this one in any source. This one has gotten more attention than average, scoring higher than 69% of its contemporaries.
We're also able to compare this research output to 179 others from the same source and published within six weeks on either side of this one. This one has gotten more attention than average, scoring higher than 73% of its contemporaries.