The Functional Roles of Glial Cells in Health and Disease

Thirty-five years ago, when Stephen Kuffler and his colleagues at Harvard initiated a new era of research on the properties and functions of neuroglial cells, very few neuro scientists were impressed at the time with the hypothesis that neuroglial cells could have another, though more subtle, role to play in the nervous system than to provide static support to neurons. Today, very few neuroscientists are unaware of the fact that multiple interactions between neurons and glial cells have been described, and that they consti tute the basis for understanding the function and the pathology of the nervous system. Glial cells outnumber neurons and make up about one-half of the bulk of the nervous system. They are divided into two major classes: first, the macroglia, which include astrocytes and oligodendrocytes in the central nervous system, and the Schwann cells in the peripheral nervous system; and second, the microglial cells. These different classes of glial cells have different functions and contribute in different ways in the devel opment, function, and the pathology of the nervous system.

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This book, which takes as its focus the biology and pathology of glial cells, pays special attention to the issues concerning the cellular and molecular interactions occurring between glia and neurons. Research over the last 30 years has shown that, contrary to previously held conceptions of the role of glial cells as being of secondary importance to that of neurons, they are major constituents of the nervous system, playing a pivotal role during development and adulthood. Moreover, recent evidence suggests that glial cells are involved in a number of disease states, some of which are still incurable, such as Alzheimer's disease, multiple sclerosis and other central and peripheral neuropathies. It is also well known that Schwann cells, the major glial cells of the peripheral nervous system, are unique in their ability to sustain and promote regeneration not only of peripheral but also of central neurons after traumatic injury. Thus the relatively new idea of repairing CNS damage through the transplantation of glial cells is an approach with great clinical potential. Bringing together contributions from expert researchers in the field, this is an informative and forward thinking approach to a continuously expanding field.

Contenu
I. Glial Cell Development.- 1. Developmental Regulation in the Schwann Cell Lineage.- 2. Transcriptional Regulation of the POU Gene Oct-6 in Schwann Cells.- 3. Glia Development in the Embryonic CNS of Drosophila.- 4. Role and Mechanism of Action of Glial Cell Deficient/Glial Cell Missing (Glide/gcm),the Fly Glial Promoting Factor.- II. Glia in Neurotransmission, Neuromodulation, and Neuron Survival.- 5. Expression and Functional Analysis of Glutamate Receptors in Glial Cells.- 6. Astrocytes as Active Participants of Glutamatergic Function and Regulators of Its Homeostasis.- 7. Glia-Neuron Interaction by High-Affinity Glutamate Transporters in Neurotransmission.- 8. On How Altered Glutamate Homeostasis May Contribute to Demyelinating Diseases of the CNS.- 9. Possible Role of Microglial Prostanoids and Free Radicals in Neuroprotection and Neurodegeneration.- III. Glia, Inflammation, and Cytokines.- 10. The Role of Microglia and Astrocytes in CNS Immune Surveillance and Immunopathology.- 11. The Role of Chemokines in the Pathogenesis of Multiple Sclerosis.- 12. Humoral and Cellular Immune Functions of Cytokine-Treated Schwann Cells.- 13. Axotomy-Induced Glial Reactions in Normal and Cytokine Transgenic Mice.- IV. Glia in CNS Plasticity and Regeneration.- 14. Contribution of Astrocytes to Activity-Dependent Structural Plasticity in the Adult Brain.- 15. The Role of Oligodendrocytes and Oligodendrocyte Progenitors in CNS Remyelination.- 16. Growth Promoting and Inhibitory Effects of Glial Cells in the Mammalian Nervous System.- 17. Neurite Outgrowth Inhibitors in Gliotic Tissue.- V. Transgenic Models of Human Myelin Diseases.- 18. Connexin32 in Hereditary Neuropathies.- 19. Genetic Analysis of Myelin Galactolipid function.- 20. Transgenic Models of TNF Induced Demyelination.- 21. Dysmyelination in Mice and the Proteolipid Protein Gene Family.- VI. Neuron-Glial Communications Neurotrophins and Cell Adhesion Molecules.- 22. Neurotrophins in Cell Survival/Death Decisions.- 23. Neuregulin in Neuron/Glial Interactions in the Central Nervous System: GGF2 Diminishes Autoimmune Demyelination, Promotes Oligodendrocyte Progenitor Expansion, and Enhances Remyelination.- 24. Adhesion Molecule Expression and Phenotype of Glial Cells in the Olfactory Tract.- 25. Bidirectional Signaling between Neurons and Glial Cells via the F3 Neuronal Adhesion Molecule.- VII. Connexins and Information Transfer through Glia.- 26. Connexins and Information Transfer through Glia.- 27. Gap Junctions in Glia: Types, Roles, and Plasticity.- 28. Metabolic Coupling and the Role Played by Astrocytes in Energy Distribution and Homeostasis.- 29. Consequences of Impaired Gap Junctional Communication in Glial Cells.- List of Contributors.