Primary Glial And Immune Cell Pathology In Neurodegenerative Diseases

The book will highlight the role played by glial cells in the central and peripheral nervous systems in both healthy and unhealthy individuals. Among all processes involved, we will discuss the importance of the enteric nervous system in the control of gut homeostasis, in the interaction with the immune system, and its participation in pathological conditions such as metabolic syndrome. We will also look at the relevance of astrocytes during synaptic transmission and the regulation of plasticity by releasing gliotransmitters. Ultimately, we will highlight the influence of astrocytes during the development of a number of neurodegenerative diseases, such as multiple sclerosis and Alzheimer’s disease, focusing on how the serum levels of the astrocytic protein S100B can be used as a biomarker for clinical decisions.

Microglia are essential for the development and function of the adult brain. Their ontogeny, together with the absence of turnover from the periphery and the singular environment of the central nervous system (CNS), make microglia a unique cell population compared to other tissue-macrophages. The unique properties and functions of microglial cells, such as their role in synaptic pruning or the exceptional capacity to scan the brain parenchyma and rapidly react to its perturbations, have emerged in recent years. In the coming years, understanding how microglia acquire and maintain their unique profiles in order to fulfil distinct tasks in the healthy CNS and how these are altered in disease, will be essential to develop strategies to diagnose or treat CNS disorders with an immunological component. This Research Topic covers several aspects of microglial biology, ranging from their origin and the functional role of microglia during development and lifespan, their molecular properties compared with other brain and peripheral immune cells to microglial phenotypes and functional states in neurodegenerative diseases and brain tumours. In conclusion, the present Research Topic provides a comprehensive overview of our current understanding of several cellular and molecular mechanisms that make microglia a unique immune cell population within the healthy CNS as well as under inflammatory, neurodegenerative and tumorigenic processes.

Immune responses within the brain are still scarcely explored. Nerve tissue damage is accompanied by the activation of glial cells, primarily microglia and astroglia, and such activation is responsible for the release of cytokines and chemokines that maintain the local inflammatory response and actively recruit lymphocytes and monocytes to the damaged areas. Theoretically, these responses are designed to repair the brain damage. However, alterations, or a chronic perpetuation of these responses may underlie a number of neuro-pathologies. It is thought that each inflammatory scenario within the brain have a specific biochemical footprint characterized by the release of determined cytokines, chemokines and growing factors able to define particular immunological responses. Alongside, glial cells transform their cell body, become larger and develop higher number of branches adopting an active morphological phenotype. These changes are related with the search of interactions with other cells, such as bystander resident cells of the brain parenchyma, but also cells homing from the blood stream. In this process, microglia and astrocytes communicates with other cells by the formation of specific intercellular connections that are still poorly understood. These interactions are complex and entail the arrangement of cytoskeletal compounds, secretory and phagocytic domains. In this particular crosstalk there is a two-way communication in which glial cells and target cells come together establishing interfaces with specific information exchange. This way, glial cells orchestrate the particular response recruiting cellular subsets within the central nervous system and organizing the resolution of the brain damage. In this Frontiers Research Topic, we compile a selection of articles unfolding diverse aspects of glial-derived inflammation, focused on neurodegenerative diseases and other nervous system disorders, with special emphasis on microglia/macrophages as leading actors managing neuro-immunity.

The brain has long been considered an immune privileged organ, meaning that inflammatory cells are excluded due to a relatively impenetrable blood brain barrier (BBB). However, this is not to say that the central nervous system is incapable of eliciting immune responses, as resident inflammatory cells exist within the brain parenchyma. Microglia have long been thought to be the brain's resident immune cell with myeloid lineage similar to monocytes and macrophages. In this volume, the authors review the current state of knowledge with regard to immune responses and cell-cell interactions as they pertain to a variety of neurodegenerative diseases. The changing role of inflammation with development is considered. They also present a summary of the various therapeutic strategies employed both in the laboratory and at the clinical level.

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 comprehensive reference provides a detailed overview of current concepts regarding the cause of Parkinson's disease-emphasizing the issues involved in the design, implementation, and analysis of epidemiological studies of parkinsonism.

In 1851, Heinrich Müller discovered what he called "radial fibers" and what we now call Müller cells, as the principal glial cells of the vertebrate retina. Later on, other glial cell types were found in the retina, including astrocytes, microglia, and even oligodendrocytes. It turned out that retinal glial cells are essential constituents of the tissue. For instance, Müller cells appear to constitute the "core" of columnar units of clonally and functionally related groups of neurons. Their primary function is to support neuronal functioning by guiding the light towards the photoreceptor cells, removing excess neurotransmitter molecules from extracellular space, and performing efficient clearance of excess extracellular potassium ions. The latter two functions are also crucial for neuronal survival and are coupled to water clearance which is also essential. Müller cells are capable of "sensing" neuronal activity and modifying it by the release of signal substances (gliotransmitters). In cases of retinal injuries the Müller cells become reactive, and all above-mentioned functions are impaired. However, such de-differentiated Müller cells may proliferate, and may even serve as stem cells for the regeneration of a damaged retina. As well as the Müller cells, retinal astrocytes and microglial cells are important players in retinal development and function. This book gives a comprehensive survey of the present knowledge on retinal glia.