Neuroscience
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In this review we discuss the possibility that the phenomenon of microglial priming can be explained by the mechanisms that underlie trained immunity. The latter involves the enhancement of inflammatory responses by epigenetic mechanisms that are mobilized after first exposure to an inflammatory stimulus. These mechanisms include long-lasting histone modifications, including H3K4me1 deposition at latent enhancer regions. Although such changes may be beneficial in peripheral infectious disease, in the context of microglial priming they may drive increased microglia reactivity that is damaging in diseases of brain aging.
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Extracellular vesicles, including exosomes and microvesicles, are small, nano-to-micrometer vesicles that are released from cells. While initially observed in immune cells and reticulocytes as vesicles meant to remove archaic proteins, now they have been observed in almost all cell types of multicellular organisms. ⋯ Recent literature supports a critical role for extracellular vesicles in mediating complex and coordinated communication among neurons, astrocytes and microglia, both in the healthy and in the diseased brain. In this review, we focus on the biogenesis and function of microglia-related extracellular vesicles and focus on their putative role in Alzheimer's disease pathology.
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Review
Physiological Interactions between Microglia and Neural Stem Cells in the Adult Subependymal Niche.
Microglia are the prototypical innate immune cells of the central nervous system. They constitute a unique type of tissue-resident mononuclear phagocytes which act as glial cells. Elegant experiments in the last few years have revealed the origin, extraordinary molecular diversity, and phenotypic plasticity of these cells and how their potential relates to both immune and non-immune actions in the normal and diseased brain. ⋯ Recent data indicate that microglial cells are distinct cellular elements of these neurogenic niches where they regulate different aspects of stem cell biology. Interestingly, microglial and neural stem cells are specified very early in fetal development and persist as self-renewing populations throughout life, suggesting potential life-long interactions between them. We aim at reviewing these interactions in one neurogenic niche, the subependymal zone.
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Microglia are instrumental for recognition and elimination of amyloid β1-42 oligomers (AβOs), but the long-term consequences of AβO-induced inflammatory changes in the brain are unclear. Here, we explored microglial responses and transciptome-level inflammatory signatures in the rat hippocampus after chronic AβO challenge. Middle-aged Long Evans rats received intracerebroventricular infusion of AβO or vehicle for 4 weeks, followed by treatment with artificial CSF or MCC950 for the subsequent 4 weeks. ⋯ Furthermore, MCC950 abrogated AβO-invoked reduction of serum IL-10. These findings provide evidence that in response to AβO infusion microglia change their phenotype, but the resulting inflammatory changes are sustained for at least one month after the end of AβO challenge. Lasting NLRP3-driven inflammatory alterations and altered hippocampal gene expression contribute to spatial memory decline.