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The impact of metallothionein-II on microglial response to tumor necrosis factor-alpha (TNFα) and downstream effects on neuronal regeneration

Overview of attention for article published in Journal of Neuroinflammation, February 2018
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  • Above-average Attention Score compared to outputs of the same age (60th percentile)
  • Above-average Attention Score compared to outputs of the same age and source (60th percentile)

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Title
The impact of metallothionein-II on microglial response to tumor necrosis factor-alpha (TNFα) and downstream effects on neuronal regeneration
Published in
Journal of Neuroinflammation, February 2018
DOI 10.1186/s12974-018-1070-3
Pubmed ID
Authors

Jacqueline Y. K. Leung, William R. Bennett, Anna E. King, Roger S. Chung

Abstract

The extracellular environment plays an important role in supporting the regeneration of axons after injury. Metallothionein-II (MTII) is a metal-binding protein known for its neuroprotective effect by directly stimulating the growth of axons after injury. Previous studies have shown that MTII also modulates the response of astrocytes and microglia after injury. However, a detailed analysis describing how MTII modulates the interaction between microglia and neurons is lacking. We introduced fluorescently labelled MTII into the cortex at the time of needlestick injury to investigate the cellular uptake of MTII using immunohistochemistry with antibodies against cell-type-specific markers. The role of MTII in modulating the effect of microglia on axon outgrowth following an inflammatory response is further investigated using a co-culture model involving primary rodent microglia pre-treated with TNFα and primary rodent cortical neurons. The axon lengths were assessed 24 h after the plating of the neurons onto treated microglia. We also utilised siRNA to knockdown the expression of LRP1, which allows us to investigate the role of LRP1 receptors in the MTII-mediated effect of microglia on axon outgrowth. Fluorescently labelled MTII was found to be associated with neurons, astrocytes and microglia following injury in vivo. Microglia-neuron co-culture experiments demonstrated that exogenous MTII altered the response of microglia to TNFα. The neurons plated onto the TNFα-stimulated microglia pre-treated with MTII have shown a significantly longer axonal length compare to the TNFα-stimulated microglia without the MTII treatment. This suggested that MTII reduce cytokine-stimulated activation of microglia, which would ordinarily impair neurite outgrowth. This inhibitory effect of MTII on activated microglia was blocked by siRNA-mediated downregulation of LRP1 receptor expression in microglia, suggesting that MTII acts via the LRP1 receptor on microglia. This study demonstrates that exogenous MTII acts via the LRP1 receptor to alter the inflammatory response of microglia following TNFα stimulation, providing a more supportive environment for axon growth.

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Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 24 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 24 100%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 5 21%
Student > Bachelor 3 13%
Lecturer > Senior Lecturer 2 8%
Student > Master 2 8%
Professor 2 8%
Other 1 4%
Unknown 9 38%
Readers by discipline Count As %
Neuroscience 8 33%
Agricultural and Biological Sciences 2 8%
Biochemistry, Genetics and Molecular Biology 2 8%
Unspecified 1 4%
Medicine and Dentistry 1 4%
Other 1 4%
Unknown 9 38%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 4. 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 09 March 2018.
All research outputs
#7,299,191
of 23,025,074 outputs
Outputs from Journal of Neuroinflammation
#1,197
of 2,655 outputs
Outputs of similar age
#128,057
of 330,913 outputs
Outputs of similar age from Journal of Neuroinflammation
#27
of 69 outputs
Altmetric has tracked 23,025,074 research outputs across all sources so far. This one has received more attention than most of these and is in the 67th percentile.
So far Altmetric has tracked 2,655 research outputs from this source. They typically receive more attention than average, with a mean Attention Score of 7.6. This one has gotten more attention than average, scoring higher than 54% 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 330,913 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 60% of its contemporaries.
We're also able to compare this research output to 69 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 60% of its contemporaries.