Neuronal synapse formation induced by microglia and interleukin 10

• Published in: PloS one Vol. 8; no. 11; p. e81218
• Main Authors: Lim, So-Hee, Park, Eunha, You, Boram, Jung, Youngseob, Park, A-Reum, Park, Sung Goo, Lee, Jae-Ran
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 22.11.2013; Public Library of Science (PLoS)
• Subjects: Animals; Animals, Newborn; Antibodies; Biotechnology; Brain; Brain research; Brain-derived neurotrophic factor; Cell culture; Culture media; Cytokines; Dendritic spines; External stimuli; Gene Expression; Gene Knockdown Techniques; Hippocampus; Hippocampus - cytology; Hippocampus - metabolism; Hostages; Immunoglobulins; Interleukin; Interleukin 10; Interleukin 10 receptors; Interleukin-10 - metabolism; Interleukin-10 - pharmacology; Interleukin-1beta - metabolism; Interleukin-1beta - pharmacology; Interleukins; Kinases; Lipopolysaccharides; Media (culture); Microglia; Microglia - metabolism; Neuroeffector Junction - drug effects; Neuroeffector Junction - metabolism; Neurons; Neurophysiology; Phosphatase; Pretreatment; Proteins; Proteomics; Pyramidal Cells - metabolism; Rats; Receptors; Receptors, Interleukin-10 - genetics; Receptors, Interleukin-10 - metabolism; Recombinant proteins; Rodents; Synapses; Synaptogenesis
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0081218

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 1β 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.