File Name: aggrecan is expressed by embryonic brain glia and regulates astrocyte development .zip
Synapses are specialized structures that mediate rapid and efficient signal transmission between neurons and are surrounded by glial cells. Astrocytes develop an intimate association with synapses in the central nervous system CNS and contribute to the regulation of ion and neurotransmitter concentrations. Together with neurons, they shape intercellular space to provide a stable milieu for neuronal activity. Extracellular matrix ECM components are synthesized by both neurons and astrocytes and play an important role in the formation, maintenance, and function of synapses in the CNS. The components of the ECM have been detected near glial processes, which abut onto the CNS synaptic unit, where they are part of the specialized macromolecular assemblies, termed perineuronal nets PNNs.
Proteoglycans PGs regulate diverse functions in the central nervous system CNS by interacting with a number of growth factors, matrix proteins, and cell surface molecules. The functionality of these PGs is to a large extent dictated by the fine sulfation patterns present on their glycosaminoglycan GAG chains. In the past 15 years, there has been a significant expansion in our knowledge on the role of HS and CS chains in various neurological processes, such as neuronal growth, regeneration, plasticity, and pathfinding. However, defining the relation between distinct sulfation patterns of the GAGs and their functionality has thus far been difficult. With the emergence of novel tools for the synthesis of defined GAG structures, and techniques for their characterization, we are now in a better position to explore the structure-function relation of GAGs in the context of their sulfation patterns. In this review, we discuss the importance of GAGs on CNS development, injury, and disorders with an emphasis on their sulfation patterns. Glycosaminoglycans GAGs are a family of linear, sulfated polysaccharides that are associated with central nervous system CNS development, maintenance, and disorders.
Proteoglycans, as part of the extracellular or cell-surface milieu of most tissues and organ systems, play important roles in morphogenesis by modulating cell-matrix or cell-cell interactions, cell adhesiveness, or by binding and presenting growth and differentiation factors. Chondroitin sulfate proteoglycans which constitute the major population of proteoglycans in the central nervous system may influence formation of neuronal nuclei, establishment of boundaries for axonal growth and act as modulators of neuronal outgrowth during brain development, as well as during regeneration after injury. There is a paucity of information on the role of chondroitin sulfate proteoglycans in central nervous system organogenesis. In the chick embryo, aggrecan has a regionally specific and developmentally regulated expression profile during brain development. By Northern and Western blot analysis, aggrecan expression is first detected in chick brain on embryonic day 7 E7 , increases from E7 to E13, declines markedly after E16, and is not evident in hatchling brains.
Glial cells in the central nervous system CNS contribute to formation of the extracellular matrix, which provides adhesive sites, signaling molecules, and a diffusion barrier to enhance efficient neurotransmission and axon potential propagation. In the normal adult CNS, the extracellular matrix ECM is relatively stable except in selected regions characterized by dynamic remodeling. However, after trauma such as a spinal cord injury or cortical contusion, the lesion epicenter becomes a focus of acute neuroinflammation. An advantage of this response is to limit the invasion of damaging cells and diffusion of toxic molecules into the spared tissue regions, but this occurs at the cost of inhibiting migration of endogenous repair cells and preventing axonal regrowth. This article highlights structural and functional features of the normal adult CNS ECM and then focuses on the reactions of glial cells and changes in the perilesion border that occur following spinal cord or contusive brain injury.
Research of the past 25 years has shown that astrocytes do more than participating and building up the blood-brain barrier and detoxify the active synapse by reuptake of neurotransmitters and ions. Indeed, astrocytes express neurotransmitter receptors and, as a consequence, respond to stimuli. Within the tripartite synapse, the astrocytes owe more and more importance. Besides the functional aspects the differentiation of astrocytes has gained a more intensive focus. Specific differentiation of neural stem cells toward the astroglial lineage is performed as a multi-step process.