Microglia, the resident immune effective cells of the central nervous system, play crucial roles in mediating immune-related process. It becomes activated quickly in response to even minor pathological insults and participates in series of immune responses. Under physiological conditions, most microglia stay in a typical resting state, with ramified processes continuously extending and retracting from surrounding neural tissues, suggesting an important function of resting microglia. Recent studies indicate that resting microglia can regulate many physiological processes, including neural development, neural circuit formation, neuronal activity and plasticity, and animal grooming behavior. Here, we review the properties of resting microglia and further discuss how microglia participate in the above-mentioned functional regulation under physiological conditions.
Animals ; Central Nervous System ; cytology ; Humans ; Microglia ; immunology ; physiology

Naegleria fowleri, a ubiquitous free-living ameba, causes fatal primary amebic meningoencephalitis in humans. N. fowleri trophozoites are known to induce cytopathic changes upon contact with microglial cells, including necrotic and apoptotic cell death and pro-inflammatory cytokine release. In this study, we treated rat microglial cells with amebic lysate to probe contact-independent mechanisms for cytotoxicity, determining through a combination of light microscopy and scanning and transmission electron microscopy whether N. fowleri lysate could effect on both necrosis and apoptosis on microglia in a time- as well as dose-dependent fashion. A 51Cr release assay demonstrated pronounced lysate induction of cytotoxicity (71.5%) toward microglial cells by 24 hr after its addition to cultures. In an assay of pro-inflammatory cytokine release, microglial cells treated with N. fowleri lysate produced TNF-alpha, IL-6, and IL-1beta, though generation of the former 2 cytokines was reduced with time, and that of the last increased throughout the experimental period. In summary, N. fowleri lysate exerted strong cytopathic effects on microglial cells, and elicited pro-inflammatory cytokine release as a primary immune response.
Animals ; *Cell Death ; Chromium Radioisotopes/metabolism ; Cytokines/*secretion ; Humans ; Microglia/cytology/immunology/*physiology ; Microscopy ; Naegleria fowleri/*pathogenicity ; Rats ; Staining and Labeling

A degree of brain inflammation is required for repair of damaged tissue, but excessive inflammation causes neuronal cell death. Here, we observe that IL-10 is expressed in LPS-injected rat cerebral cortex, contributing to neuronal survival. Cells immunopositive for IL-10 were detected as early as 8 h post-injection and persisted for up to 3 d, in parallel with the expression of IL-1beta, TNF-alpha, and iNOS. Double immunofluorescence staining showed that IL-10 expression was localized mainly in activated microglia. Next, we examined the neuroprotective effects of IL-10 using IL-10 neutralizing antibody (IL-10NA). Blockade of IL-10 action caused a significant loss of neurons both 3 d and 7 d after LPS injection. Further, the induction of mRNA species encoding IL-1beta, TNF-alpha, and iNOS, reactive oxygen species (ROS) production, and NADPH oxidase activation, increased after co-injection of LPS and IL-10NA, compared to the levels seen after injection of LPS alone. Taken together, these results clearly suggest that LPS-induced endogenous expression of IL-10 in microglia contributes to neuronal survival by inhibiting brain inflammation.
Animals ; Cerebral Cortex/drug effects/*pathology ; Fluorescent Antibody Technique ; Interleukin-10/immunology/*physiology ; Lipopolysaccharides/*pharmacology ; Microglia/cytology/*metabolism ; Nerve Degeneration/pathology/*prevention & control ; Neurons/cytology/drug effects/*metabolism ; Nitric Oxide Synthase/genetics/metabolism ; Rats ; Rats, Sprague-Dawley ; Reactive Oxygen Species/metabolism