Format

Send to

Choose Destination
Sci Rep. 2015 Jan 23;5:7989. doi: 10.1038/srep07989.

Neuronal exosomes facilitate synaptic pruning by up-regulating complement factors in microglia.

Author information

1
Laboratory of Immune Network, WPI Immunology Frontier Research Center (IFReC), Osaka University, 3-1 Yamada-oka, Suita, Osaka 565-0871, Japan.
2
Quantitative Immunology Research Unit, WPI Immunology Frontier Research Center (IFReC), Osaka University, 3-1 Yamada-oka, Suita, Osaka 565-0871, Japan.
3
1] Laboratory of Immune Network, WPI Immunology Frontier Research Center (IFReC), Osaka University, 3-1 Yamada-oka, Suita, Osaka 565-0871, Japan [2] PRESTO, Japan Science and Technology Agency (JST), 4-1-8 Honcho, Kawaguchi, Saitama 332-0012, Japan.

Abstract

Selective elimination of synaptic connections is a common phenomenon which occurs during both developmental and pathological conditions. Glial cells have a central role in the pruning of synapses by specifically engulfing the degenerating neurites of inappropriate connections, but its regulatory mechanisms have been largely unknown. To identify mediators of this process, we established an in vitro cell culture assay for the synapse elimination. Neuronal differentiation and synapse formation of PC12 cells were induced by culturing the cells with nerve growth factor (NGF) in a serum-free medium. To trigger synapse elimination, the NGF-containing medium was replaced with DMEM containing 10% FBS, and the neurites of PC12 cells degenerated within two days. Co-culturing with MG6 cells, a mouse microglial cell line, accelerated the removal of degenerating neurites of PC12 cells by phagocytosis. When MG6 cells were pre-incubated with exosomes secreted from the differentiated PC12 cells after depolarization, the removal was further accelerated by increasing the expression levels of complement component 3 in the MG6 cells. These results define a role for exosomes as a regulator of synapse elimination and clarify a novel mechanism whereby active synapses promote the pruning of inactive ones by stimulating microglial phagocytosis with exosomes.

PMID:
25612542
PMCID:
PMC4303875
DOI:
10.1038/srep07989
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Nature Publishing Group Icon for PubMed Central
Loading ...
Support Center