Partial Depletion of Peripheral M1 Macrophages Reverses Motor Deficits in MPTP-Treated Mouse by Suppressing Neuroinflammation and Dopaminergic Neurodegeneration
Aijuan Yan, Yu Zhang, Jingya Lin, Lu Song, Xijin Wang, Zhenguo Liu
Abstract
Background: Neuroinflammation plays an important role in the pathogenesis of Parkinson's disease (PD). Inflammatory cytokines in the peripheral immune system can induce neuroinflammation in central nervous system (CNS). Whether the peripheral immune system is involved in PD is unclear. The present study investigated the contribution of the peripheral immune system to the neuronal loss in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP) model of PD. Methods: MPTP was intraperitoneally injected into mice to generate a PD model. Mice received clodronate liposomes every 3 days to deplete peripheral macrophages. The percentages of macrophages were measured by flow cytometry at 1, 3, and 7 days after MPTP injection. Neurobehavioral parameters, protein expression, inflammatory cytokines release, and microglia activation were measured by the open field test, western blotting, quantitative polymerase chain reaction (qPCR), and immunofluorescence staining, respectively at 7 days after MPTP injection. Results: Our study revealed that intraperitoneal injection of MPTP could increase peripheral M1 macrophages levels. It also can induce T cells infiltration and cytokine release. Depletion of M1 macrophages by clodronate liposomes suppressed these inflammatory effects and blunted the loss of TH+ nigral neurons and functional impairments caused by MPTP. Conclusion: Our results indicated the critical role of M1 macrophages in the pathogenesis of PD and proposed inhibition of M1 macrophages as a promising therapeutic approach for neurodegeneration.
Pharmacology, Toxicology and Pharmaceutical Science
3
8%
Immunology and Microbiology
2
5%
Other
4
11%
Unknown
6
16%
Attention Score in Context
Attention Score in Context
This research output has an Altmetric Attention Score of 11. 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 13 July 2018.
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#3,208,630
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Outputs from Frontiers in Aging Neuroscience
#1,337
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Outputs of similar age
#61,293
of 337,015 outputs
Outputs of similar age from Frontiers in Aging Neuroscience
#42
of 109 outputs
Altmetric has tracked 25,375,376 research outputs across all sources so far. Compared to these this one has done well and is in the 87th percentile: it's in the top 25% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 5,481 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 14.4. This one has gotten more attention than average, scoring higher than 74% of its peers.
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We're also able to compare this research output to 109 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 59% of its contemporaries.
