Microglia

These past few years have witnessed a revolution in our understanding of microglia, especially since their roles in the healthy central nervous system (CNS) have started to unravel. These cells were shown to actively maintain health, in concert with neurons and other types of CNS cells, providing further insight into their involvement with diseases. Edited by two pioneers in the field, Marie-Ève Tremblay and Amanda Sierra, Microglia in health and disease aims to share with the broader scientific community some of the recent discoveries in microglia research, from a broad perspective, with a collection of 19 chapters from 52 specialists working in 11 countries across 5 continents. To set microglia on the stage, the book begins by explaining briefly who they are, what they do in the healthy and diseased CNS, and how they can be studied. The first section describes in more details their physiological roles in the maturation, function, and plasticity of the CNS, across development, adolescence, adulthood, neuropathic pain, addiction, and aging. The second section focuses on their implication in pathological conditions impairing the quality of life: neurodevelopmental and neuropsychiatric disorders, AIDS, and multiple sclerosis; and in leading causes of death: ischemia and stroke, neurodegenerative diseases, as well as trauma and injury.

This book presents a comprehensive toolkit of versatile techniques for studying microglia under different experimental settings along with a brief summary of knowledge, accumulated in microglial research over the last decades. Beginning with recently discovered roles of microglia in health and disease, the volume continues by covering in vitro analyses of microglia, in vivo studies, and “omics” analyses. Written for the highly successful Methods in Molecular Biology series, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and tips on troubleshooting and avoiding known pitfalls. Authoritative and cutting-edge, Microglia: Methods and Protocols serves as a vital guide to these important cells and an inspiration for scientists interested in expanding our knowledge of their role in the nervous system.

The study of microglial cells has recently gained importance for those researching degeneration and regeneration. Microglia in the regenerating and degenerating CNS supports the assertion that understanding microglial biology could perhaps be pivotal for unraveling the pathogenetic mechanisms that underlie Alzheimer's disease, In addition, microglia are also critical for understanding the sequelae of traumatic brain and spinal cord injury, and for the important post-traumatic repair processes. This book gives an up to date account of the role of microglia in degeneration and regeneration of the nervous system and reviews their cell function and physiology.

Microglial cells play a vital role in the innate immune response occurring in the Central Nervous System (CNS). Under physiologic conditions, microglia dynamically patrol the brain parenchyma and participate in the remodeling of active neuronal circuits. Accordingly, microglia can boost synaptic plasticity by removing apoptotic cells and by phagocytizing axon terminals and dendritic spines that form inappropriate neural connections. Upon brain and spinal cord injury or infection, microglia act as the first line of immune defense by promoting the clearance of damaged cells or infectious agents and by releasing neurotrophins and/ or proneurogenic factors that support neuronal survival and regeneration. Recently, two main pathways were suggested for microglia activation upon stimuli. Classical activation is induced by Toll-like receptor agonists and Th1 cytokines and polarizes cells to an M1 state, mainly leading to the release of TNF-alpha, IL-6 and nitric oxide and to grave neural damage. Alternative activation is mediated by Th2 cytokines and polarizes cells to an M2a state inducing the release of antiinflammatory factors. These findings have further fueled the discussion on whether microglia has a detrimental or beneficial action (M1 or M2-associated phenotypes, respectively) in the diseased or injured CNS and, more importantly, on whether we can shift the balance to a positive outcome. Although microglia and macrophages share several common features, upon M1 and M2 polarizing conditions, they are believed to develop distinct phenotypic and functional properties which translate into different patterns of activity. Moreover, microglia/macrophages seem to have developed a tightly organized system of maintenance of CNS homeostasis, since cells found in different structures have different morphology and specific function (e.g. meningeal macrophages, perivascular macrophages, choroid plexus macrophages). Nevertheless, though substantial work has been devoted to microglia function, consensus around their exact origin, their role during development, as well as the exact nature of their interaction with other cells of the CNS has not been met. This issue discusses how microglial cells sustain neuronal activity and plasticity in the healthy CNS as well as the cellular and molecular mechanisms developed by microglia in response to injury and disease. Understanding the mechanisms involved in microglia actions will enforce the development of new strategies to promote an efficient CNS repair by committing microglia towards neuronal survival and regeneration.

Microglia are largely known as the major orchestrators of the brain inflammatory response. As such, they have been traditionally studied in various contexts of disease, where their activation has been assumed to induce a wide range of detrimental effects. In the last few years, a series of discoveries have challenged the current view of microglia, showing their active and positive contribution to normal brain function. This Research Topic reviewed the novel physiological roles of microglia in the developing, mature and aging brain, under non-pathological conditions. In particular, this Research Topic discussed the cellular and molecular mechanisms by which microglia contribute to the formation, pruning and plasticity of synapses; the regulation of adult neurogenesis as well as hippocampal learning and memory; among other important roles. Because these novel findings defy our understanding of microglial function in health as much as in disease, this Research Topic also summarized the current view of microglial nomenclature, phenotypes, origin and differentiation, and contribution to various brain pathologies. Additionally, novel imaging approaches and molecular tools to study microglia in their non-activated state have been discussed. In conclusion, this Research Topic seeked to emphasize how the current research in neuroscience is challenged by never-resting microglia.

Microglia-mediated neuroinflammation is one of the shared prominent hallmarks among various forms of neurodegeneration. Depending on the milieu in which microglia become activated, the polarization of microglia shows to be heterogeneous with diverse functional phenotypes that range from pro-inflammatory phenotypes to immunosuppressive phenotypes. Therefore, targeting microglial polarization holds great promise for the treatment of neurodegeneration. This eBook focuses on the potential mechanisms of microglial polarization that are critically associated with a broad spectrum of neurodegenerative diseases, including Parkinson’s disease (PD), Alzheimer’s disease (AD), Amyotrophic lateral sclerosis (ALS), Huntington’s disease (HD), Traumatic brain injury (TBI), glaucomatous neurodegeneration and prion diseases. This topic also involves the therapeutic targeting of microglial polarization by nutritional and pharmacological modulators. Moreover, this topic describes advanced technologies employed for studying microglia. Age-related changes in microglia functions are also discussed. Overall, this eBook provides comprehensive understandings of microglial polarization in the course of neurodegeneration, linking with aging-related microglial alterations and technologies developed for microglial studies. Hopefully, it will also give comprehensive insights into various aspects of therapeutic treatment for neurodegeneration, through targeting microglial polarization.

The genetic, molecular, and cellular mechanisms of neural development are essential for understanding evolution and disorders of neural systems. Recent advances in genetic, molecular, and cell biological methods have generated a massive increase in new information, but there is a paucity of comprehensive and up-to-date syntheses, references, and historical perspectives on this important subject. The Comprehensive Developmental Neuroscience series is designed to fill this gap, offering the most thorough coverage of this field on the market today and addressing all aspects of how the nervous system and its components develop. Particular attention is paid to the effects of abnormal development and on new psychiatric/neurological treatments being developed based on our increased understanding of developmental mechanisms. Each volume in the series consists of review style articles that average 15-20pp and feature numerous illustrations and full references. Volume 1 offers 48 high level articles devoted mainly to patterning and cell type specification in the developing central and peripheral nervous systems. Series offers 144 articles for 2904 full color pages addressing ways in which the nervous system and its components develop Features leading experts in various subfields as Section Editors and article Authors All articles peer reviewed by Section Editors to ensure accuracy, thoroughness, and scholarship Volume 1 sections include coverage of mechanisms which: control regional specification, regulate proliferation of neuronal progenitors and control differentiation and survival of specific neuronal subtypes, and controlling development of non-neural cells