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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Microglia are the primary immune cells of the central nervous system. However, recent data indicate that microglia also contribute to diverse physiological and pathophysiological processes that extend beyond immune-related functions and there is a growing interest to understand the mechanisms through which microglia interact with other cells in the brain. In particular, the molecular processes that contribute to microglia-neuron communication in the healthy brain and their role in common brain diseases have been intensively studied during the last decade. ⋯ Despite the exponentially increasing knowledge about microglia, the role of these cells in health and disease is still extremely controversial and the precise molecular targets for intervention are not well defined. This is in part due to the lack of microglia-specific manipulation approaches until very recently and to the high level of complexity of the interactions between microglia and other cells in the brain that occur at different temporal and spatial scales. In this review, we briefly summarize the known physiological roles of microglia-neuron interactions in brain homeostasis and attempt to outline some major directions and challenges of future microglia research.
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Microglia are considered to be the resident macrophages of the CNS and main effector of immune brain function. Due to their essential role in the regulation of neuroinflammatory response, microglia constitute an important target for neurological diseases, such as multiple sclerosis, Alzheimer's or Parkinson's disease. The communication between neurons and microglia contributes to a proper maintenance of homeostasis in the CNS. ⋯ Specifically, the effects of CD200-CD200R in the inhibition of pro-inflammatory microglial activation will be explained, and their involvement in other functions such as homeostasis preservation, tissue repair, and brain aging, among others, will be pointed out. In addition, we will depict the effects of CD200-CD200R uncoupling in the etiopathogenesis of autoimmune and neurodegenerative diseases. Finally, we will explore how to translate the scientific evidence of CD200-CD200R interaction into possible clinical therapeutic strategies to tackle neuroinflammatory CNS diseases.
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Microglia are the principle immune cells of the brain. Once activated, microglial cells may exhibit a wide repertoire of the context-dependent profiles ranging from highly neurotoxic to more protective and pro-regenerative cellular phenotypes. While to date the mechanisms involved in the molecular regulation of the microglia polarization phenotypes remain elusive, growing evidence suggests that gender may markedly affect the inflammatory and/or glial responses following brain injuries. ⋯ Here, we review recent advances revealing microglia as an important determinant of gender differences under physiological conditions and in injured brain. We also discuss how microglia-driven innate immunity and signaling pathways might be involved in the sex-dependent responses following brain ischemic injury. Finally we describe how advanced methods such as live imaging techniques may help elucidate the role of microglia in the modulation of immune responses and gender difference after stroke.
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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.