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.

The receptor-type protein tyrosine phosphatases (RPTPs) have been linked to signal transduction, cell adhesion, and neurite extension. PTPRT/RPTPq is exclusively expressed in the central nervous system and regulates synapse formation by interacting with cell adhesion molecules and Fyn protein tyrosine kinase. Overexpression of PTPRT in cultured neurons increased the number of excitatory and inhibitory synapses by recruiting neuroligins that interact with PTPRT through their ecto-domains. In contrast, knockdown of PTPRT inhibited synapse formation and withered dendrites. Incubation of cultured neurons with recombinant proteins containing the extracellular region of PTPRT reduced the number of synapses by inhibiting the interaction between ecto-domains. Synapse formation by PTPRT was inhibited by phosphorylation of tyrosine 912 within the membrane-proximal catalytic domain of PTPRT by Fyn. This tyrosine phosphorylation reduced phosphatase activity of PTPRT and reinforced homophilic interactions of PTPRT, thereby preventing the heterophilic interaction between PTPRT and neuroligins. These results suggest that brain-specific PTPRT regulates synapse formation through interaction with cell adhesion molecules, and this function and the phosphatase activity are attenuated through tyrosine phosphorylation by the synaptic tyrosine kinase Fyn.

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BackgroundSerrated lesions of the colorectum as categorized by pathology include hyperplastic polyps, sessile serrated adenomas without dysplasia, and traditional serrated adenomas with dysplasia. The aim of this study was to investigate the prevalence of various subtypes of serrated lesions by age.MethodsIn this study, 28,544 consecutive asymptomatic patients (aged 22–88 years) were evaluated during health check-ups involving colonoscopies performed by gastroenterologists at a single institution from 2005 to 2012.ResultsThe adenoma detection rate during colonoscopies for patients aged ≥50 years was 31.8% (25.0–35.8%). The serrated lesion detection rate for patients aged ≥50 years was 15.3% (10.5–19.6%). Serrated lesions were detected in 15.1% of all patients with subtype prevalences of 14.7% for hyperplastic polyps, 0.5% for sessile serrated adenomas, and 0.1% for traditional serrated adenomas. The prevalence of conventional adenomas increased sharply with age (5.0% in patients aged 20–29 years, 10.9% in those aged 30–39 years, 21.8% in those aged 40–49 years, 29.5% in those aged 50–59 years, 36.9% in those aged 60–69 years, and 40.7% in those aged ≥70 years) (trend P = 0.027). In contrast, the prevalence of serrated lesions increased only slightly with age (10.0% in patients aged 20–29 years, 11.8% in those aged 30–39 years, 14.8% in those aged 40–49 years, 15.3% in those aged 50–59 years, 16.8% in those aged 60–69 years, and 16.4% in those aged ≥70 years) (trend P = 0.036).ConclusionsThe screening colonoscopy detection rate of serrated lesions, including sessile serrated adenomas and traditional serrated adenomas, appears to be relatively high among young patients aged <50 years.

Typical reflux symptoms can be used to distinguish patients with GERD-related NCCP from patients with NCCP, and subgrouping according to characteristic symptoms may assist the diagnosis of these patients in Korea.