The human nervous system is the organ of consciousness, cognition, ethics, and behavior; as such, it is the most intricate structure known to exist. More than one-third of the 23,000 genes encoded in the human genome are expressed in the nervous system. Each mature brain is composed of 100 billion neurons, several million miles of axons and dendrites, and >1015 synapses. Neurons exist within a dense parenchyma of multifunctional glial cells that synthesize myelin, preserve homeostasis, and regulate immune responses. Measured against this background of complexity, the achievements of molecular neuroscience have been extraordinary. Advances have occurred in parallel with the development of new enabling technologies—in bioengineering and computational sciences, imaging, and cell, molecular and chemical biology—and moving forward it is likely that the pace of new discoveries will only increase. This chapter reviews a number of the most dynamic areas in neuroscience, specifically highlighting advances in immunology and inflammation, neurodegeneration, and stem cell biology. In each of these areas, recent discoveries are providing context for an understanding of the triggers and mechanisms of disease, and offering new hope for prevention, treatment, and repair of nervous system injuries. Discussions of the neurogenetics of behavior, advances in addiction science, and diseases caused by network dysfunction can be found in Chap. 443 (Biology of Psychiatric Disorders); and new approaches to rehabilitation via harnessing of neuroplasticity, neurostimulation, and computer-brain interfaces are presented in Chap. 477 (Emerging Neurotherapeutic Technologies).
NEUROIMMUNOLOGY AND NEUROINFLAMMATION
OLIGODENDROCYTES AND MYELIN
Myelin is the multilayered insulating substance that surrounds axons and speeds impulse conduction by permitting action potentials to jump between naked regions of axons (nodes of Ranvier) and across myelinated segments. Molecular interactions between the myelin membrane and axon are required to maintain the stability, function, and normal life span of both structures. A single oligodendrocyte usually ensheaths multiple axons in the central nervous system (CNS), whereas in the peripheral nervous system (PNS), each Schwann cell typically myelinates a single axon. Myelin is a lipid-rich material formed by a spiraling process of the membrane of the myelinating cell around the axon, creating multiple membrane bilayers that are tightly apposed (compact myelin) by charged protein interactions. Several inhibitors of axon growth are expressed on the innermost (periaxonal) lamellae of the myelin membrane (see below). A number of clinically important neurologic disorders are caused by inherited mutations in myelin proteins of the CNS or PNS (Chap. 438), and constituents of myelin also have a propensity to be targeted as autoantigens in autoimmune demyelinating disorders (Chap. 436).
Premyelinating oligodendrocyte precursor cells (OPCs) are highly motile cells that migrate extensively during development and in the adult brain following injuries to the myelin sheath. OPCs migrate along the inner (or abluminal) surface of endothelial cells, a process regulated by Wnt pathway signaling and upregulation of the chemokine receptor Cxcr4 that drives their attachment and retention to the vasculature. Initial ...