Infiltration of circulating myeloid cells through CD95L contributes to neurodegeneration in mice

The Journal of Experimental Medicine
Liang GaoAna Martin-Villalba

Abstract

Neuroinflammation is increasingly recognized as a hallmark of neurodegeneration. Activated central nervous system-resident microglia and infiltrating immune cells contribute to the degeneration of dopaminergic neurons (DNs). However, how the inflammatory process leads to neuron loss and whether blocking this response would be beneficial to disease progression remains largely unknown. CD95 is a mediator of inflammation that has also been proposed as an apoptosis inducer in DNs, but previous studies using ubiquitous deletion of CD95 or CD95L in mouse models of neurodegeneration have generated conflicting results. Here we examine the role of CD95 in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridin (MPTP)-induced neurodegeneration using tissue-specific deletion of CD95 or CD95L. We show that DN death is not mediated by CD95-induced apoptosis because deletion of CD95 in DNs does not influence MPTP-induced neurodegeneration. In contrast, deletion of CD95L in peripheral myeloid cells significantly protects against MPTP neurotoxicity and preserves striatal dopamine levels. Systemic pharmacological inhibition of CD95L dampens the peripheral innate response, reduces the accumulation of infiltrating myeloid cells, and efficiently prevents MPTP...Continue Reading

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Oct 4, 2015·Biochimica Et Biophysica Acta·Peter Wieghofer, Marco Prinz
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Methods Mentioned

BETA
PCR
flow cytometry
FACS
glycosylation

Software Mentioned

ImageJ
FlowJo
ImageJ Cell Counter Plugin
GraphPad
Prism
ImageJ Threshold Color Plugin

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