RGD Reference Report - Neuronal synapse formation induced by microglia and interleukin 10. - Rat Genome Database

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Neuronal synapse formation induced by microglia and interleukin 10.

Authors: Lim, SH  Park, E  You, B  Jung, Y  Park, AR  Park, SG  Lee, JR 
Citation: Lim SH, etal., PLoS One. 2013 Nov 22;8(11):e81218. doi: 10.1371/journal.pone.0081218. eCollection 2013.
RGD ID: 11049480
Pubmed: PMID:24278397   (View Abstract at PubMed)
PMCID: PMC3838367   (View Article at PubMed Central)
DOI: DOI:10.1371/journal.pone.0081218   (Journal Full-text)

Recently, it was found that microglia regulated synaptic remodeling of the developing brain, but their mechanisms have not been well understood. In this study, the action of microglia on neuronal synapse formation was investigated, and the primary target of microglial processes was discovered. When the developing microglia were applied to cultured hippocampal neurons without direct contact, the numbers of dendritic spines and excitatory and inhibitory synapses significantly increased. In order to find out the main factor for synaptic formation, the effects of cytokines released from microglia were examined. When recombinant proteins of cytokines were applied to neuronal culture media, interleukin 10 increased the numbers of dendritic spines in addition to excitatory and inhibitory synapses. Interestingly, without external stimuli, the amount of interleukin 10 released from the intact microglia appeared to be sufficient for the induction of synaptic formation. The neutralizing antibodies of interleukin 10 receptors attenuated the induction of the synaptic formation by microglia. The expression of interleukin 10 receptor was newly found in the hippocampal neurons of early developmental stage. When interleukin 10 receptors on the hippocampal neurons were knocked down with specific shRNA, the induction of synaptic formation by microglia and interleukin 10 disappeared. Pretreatment with lipopolysaccharide inhibited microglia from inducing synaptic formation, and interleukin 1beta antagonized the induction of synaptic formation by interleukin 10. In conclusion, the developing microglia regulated synaptic functions and neuronal development through the interactions of the interleukin 10 released from the microglia with interleukin 10 receptors expressed on the hippocampal neurons.

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
regulation of synapse organization  IDA 11049480 RGD 
regulation of synapse organization  IMP 11049480 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Il10  (interleukin 10)
Il10ra  (interleukin 10 receptor subunit alpha)


Additional Information