Abstract
Over the last decade knowledge of the role of astrocytes in central nervous system (CNS) neuroinflammatory diseases has changed dramatically. Rather than playing a merely passive role in response to damage it is clear that astrocytes actively maintain CNS homeostasis by influencing pH, ion and water balance, the plasticity of neurotransmitters and synapses, cerebral blood flow, and are important immune cells. During disease astrocytes become reactive and hypertrophic, a response that was long considered to be pathogenic. However, recent studies reveal that astrocytes also have a strong tissue regenerative role. Whilst most astrocyte research focuses on modulating neuronal function and synaptic transmission little is known about the cross-talk between astrocytes and oligodendrocytes, the myelinating cells of the CNS. This communication occurs via direct cell-cell contact as well as via secreted cytokines, chemokines, exosomes, and signalling molecules. Additionally, this cross-talk is important for glial development, triggering disease onset and progression, as well as stimulating regeneration and repair. Its critical role in homeostasis is most evident when this communication fails. Here, we review emerging evidence of astrocyte-oligodendrocyte communication in health and disease. Understanding the pathways involved in this cross-talk will reveal important insights into the pathogenesis and treatment of CNS diseases.
Highlights
Astrocytes, the most abundant glial cell type in the central nervous system (CNS), have long been considered to be cells that only respond to damage in CNS diseases
Inhibition of the oligodendrocyte cholesterol synthesis pathway in mice leads to a delay in myelination suggesting cholesterol production by oligodendrocytes and astrocytes is critical for early myelination [70]
Excitotoxicity is a relevant mechanism of cell death in many disorders, and astrocyte-oligodendrocyte cross-talk plays an important role here, as astrocytes are able to create a hostile environment with glutamate and ATP which damages oligodendrocytes
Summary
Astrocytes, the most abundant glial cell type in the central nervous system (CNS), have long been considered to be cells that only respond to damage in CNS diseases. While much of the knowledge of astrocytes relates to their interaction with neurons and neuronal functions astrocytes collaborate and impact on other cells within the CNS as well, such as endothelial cells and pericytes in BBB formation They share their lineage with oligodendrocytes and interact with these myelin forming cells by sharing gap junctions allowing passage of small metabolites and molecules for communication [6]. Oligodendrocytes provide axons with trophic support and are crucial for neuronal functionality [2,7] Due to their high turnover of myelin oligodendrocytes are sensitive to reactive oxygen species and oxidative stress [7,8]. Understanding how astrocytes interact with oligodendrocytes will provide a deeper insight into the pathophysiology of neurological disorders that may elucidate new pathways to drug strategies for myelin damage in CNS diseases
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