Abstract:
:Activation of microglia resulting in exacerbated inflammation expression plays an important role in degeneration of dopaminergic (DA) neurons in the pathogenesis of Parkinson's disease (PD). However, how this enhanced inflammation is induced in microglia remains largely unclear. Here, in the mouse PD model induced by 1-methyl-4-phenyl-1,2,3,6-tetra hydropyridine (MPTP), we found that miR-7116-5p in microglia has a crucial role in this inflammation. 1-methyl-4-phenylpyridinium (MPP+ ) is uptaken by microglia through organic cation transporter 3 (OCT3) to downregulate miR-7116-5p, an miRNA found to target tumor necrosis factor alpha (TNF-α). Production of TNF-α in microglia is specifically potentiated by MPP+ via downregulation of miR-7116-5p to elicit subsequent inflammatory responses. Furthermore, enhancement of miR-7116-5p expression in microglia in mice inhibits the production of TNF-α and the activation of glia, and further prevents loss of DA neurons. Together, our studies suggest that MPP+ suppresses miR-7116-5p level in microglia and potentiates TNF-α production and inflammatory responses to contribute to DA neuron damage.
journal_name
Gliajournal_title
Gliaauthors
He Q,Wang Q,Yuan C,Wang Ydoi
10.1002/glia.23153subject
Has Abstractpub_date
2017-08-01 00:00:00pages
1251-1263issue
8eissn
0894-1491issn
1098-1136journal_volume
65pub_type
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