Plasticity Of Glial Cells In The Enteric Nervous System During Intestinal Inflammation

Enteric glial cell (EGC) markers were thoroughly characterized in the human enteric nervous system (ENS) and EGC numbers were compared in man and guinea pig. As a result, the Sox8/9/10 antibody was shown to be an excellent investigative tool to assess EGC in the ENS and the glia index was identified as the most robust quantitative descriptor within a species. Subsequently, this Sox8/9/10 was used in Crohnþs disease specimens to quantify enteric glia. In a parallel approach, interactions of EGC and the intestinal epithelial barrier were analyzed. Results from these experiments indicate a protective effect of EGCs on the intestinal epithelial barrier in intestinal inflammation. The observed expression of GDNF, NGF, NT-3 and their receptors by EGC points to promising targets for further research to elucidate the exact nature of glial-derived mucosa-protective factors.

The enteric nervous system (ENS) is a complex neural network embedded in the gut wall that orchestrates the reflex behaviors of the intestine. The ENS is often referred to as the “little brain” in the gut because the ENS is more similar in size, complexity and autonomy to the central nervous system (CNS) than other components of the autonomic nervous system. Like the brain, the ENS is composed of neurons that are surrounded by glial cells. Enteric glia are a unique type of peripheral glia that are similar to astrocytes of the CNS. Yet enteric glial cells also differ from astrocytes in many important ways. The roles of enteric glial cell populations in the gut are beginning to come to light and recent evidence implicates enteric glia in almost every aspect of gastrointestinal physiology and pathophysiology. However, elucidating the exact mechanisms by which enteric glia influence gastrointestinal physiology and identifying how those roles are altered during gastrointestinal pathophysiology remain areas of intense research. The purpose of this e-book is to provide an introduction to enteric glial cells and to act as a resource for ongoing studies on this fascinating population of glia. Table of Contents: Introduction / A Historical Perspective on Enteric Glia / Enteric Glia: The Astroglia of the Gut / Molecular Composition of Enteric Glia / Development of Enteric Glia / Functional Roles of Enteric Glia / Enteric Glia and Disease Processes in the Gut / Concluding Remarks / References / Author Biography

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.

Inflammatory bowel diseases (IBD) are chronic inflammatory conditions of the gastrointestinal (GI) tract that cause impairments in GI functions, as well as structural and functional plasticity to the innervation of gut that regulates these functions. T helper-17 lymphocytes and interleukin (IL)-17A are crucial to the pathogenesis of IBD and intestinal inflammation. Recent studies in mice report that IL-17A promotes postganglionic sympathetic neurite outgrowth, inhibits voltage-dependent Ca2+ influx and likely contributes to neuroanatomical plasticity within the inflamed GI tract. We hypothesized that IL-17A contributes to sympathetic neuroanatomical remodelling in the colon of patients with IBD and is also capable of signalling to neurons of the enteric nervous system. Mucosal biopsy supernatants from patients with Crohn's disease (CD) enhanced neurite outgrowth of mouse sympathetic neurons compared to supernatants from control patients. The enhanced outgrowth was abolished when a neutralizing IL-17A antiserum was added. Supernatants from patients with ulcerative colitis did not enhance sympathetic neurite outgrowth, but addition of the neutralizing IL-17A antiserum reduced outgrowth. Despite the growth-promoting effect of the inflammatory milieu from patients with CD, tyrosine hydroxylase-immunoreactivity, a marker of sympathetic axons, was reduced within inflamed regions of resected colon specimens from patients with CD compared to uninflamed regions and control patients without IBD. Since enteric neurons also express the IL-17 receptor-A, we examined the effect of IL-17A on myenteric neuron Ca2+ signaling and neurite outgrowth. Depolarization-induced Ca2+ signaling was doubled in IL-17A-treated neurons relative to controls. IL-17A also increased myenteric neuron neurite complexity, and promoted the proliferation of enteric glial cells. The enhanced neurite complexity was abrogated by the mitotic inhibitor cytosine arabinoside. Although the colons of mice with acute dextran sulphate sodium (DSS) colitis had an elevated amount of IL-17A, there was no difference in myenteric neuron depolarization-induced Ca2+ signaling. Myenteric neurons from mice with acute DSS colitis also had enhanced neurite outgrowth, but a reduction in glial cell proliferation compared to cultures from control mice. These findings suggest that IL-17A signals to the innervation of the gut and likely contributes to the effects of inflammation on these neural circuits.

Glial Physiology and Pathophysiology provides a comprehensive, advanced text on the biology and pathology of glial cells. Coverae includes: the morphology and interrelationships between glial cells and neurones in different parts of the nervous systems the cellular physiology of the different kinds of glial cells the mechanisms of intra- and inter-cellular signalling in glial networks the mechanisms of glial-neuronal communications the role of glial cells in synaptic plasticity, neuronal survival and development of nervous system the cellular and molecular mechanisms of metabolic neuronal-glial interactions the role of glia in nervous system pathology, including pathology of glial cells and associated diseases - for example, multiple sclerosis, Alzheimer's, Alexander disease and Parkinson's Neuroglia oversee the birth and development of neurones, the establishment of interneuronal connections (the 'connectome'), the maintenance and removal of these inter-neuronal connections, writing of the nervous system components, adult neurogenesis, the energetics of nervous tissue, metabolism of neurotransmitters, regulation of ion composition of the interstitial space and many, many more homeostatic functions. This book primes the reader towards the notion that nervous tissue is not divided into more important and less important cells. The nervous tissue functions because of the coherent and concerted action of many different cell types, each contributing to an ultimate output. This reaches its zenith in humans, with the creation of thoughts, underlying acquisition of knowledge, its analysis and synthesis, and contemplating the Universe and our place in it. An up-to-date and fully referenced text on the most numerous cells in the human brain Detailed coverage of the morphology and interrelationships between glial cells and neurones in different parts of the nervous system Describes the role og glial cells in neuropathology Focus boxes highlight key points and summarise important facts Companion website with downloadable figures and slides

The research and outcomes presented in this book gather evidence concerning both the pathogenesis and treatment of functional dyspepsia. It provides the latest information on this common non-organic disease, indicating its characteristic pathogenesis based on the brain-gut interaction and micro-environment and evidence gleaned from clinical treatment. Since the pathogenesis is associated with psychology, neurology, endocrinology and bacteriology in addition to gastroenterological physiology, it is often intractable and finding a suitable treatment rationale is challenging. Furthermore, the pathogenesis varies around the world and the efficacy of treatment using standard drugs varies among different populations worldwide; accordingly, this book highlights evidence gained in clinical trials in Japan. Functional Dyspepsia is a milestone produced by respected experts. Addressing unique topics and new findings of treatment including challenging and/or future rationales, it offers an invaluable resource for general clinicians, gastroenterologists, and basic researchers alike.