157 Astrocyte and Oligodendrocyte Crosstalk Introduction 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. This view is gradually changing with the accumulating evidence that astrocytes fulfil many functions in health, during development and in response to damage1. Astrocytes regulate processes critical for cell-cell interactions and homeostasis such as ion and water transport, pH, neuroplasticity, synapse pruning and cerebral blood flow thus providing trophic and metabolic support to all cells in the CNS. Astrocytes also play a major role in maintaining the blood-brain barrier (BBB) and blood-cerebrospinal fluid barrier. During CNS injury, infection and inflammation astrocytes produce a wide range of pro-inflammatory factors including chemokines, cytokines, increased expression of innate immune receptors and molecules including MHC-II2-5. On the other hand, astrocytes produce anti-inflammatory cytokines, heat shock proteins and neuroprotective factors aiding in processes such as neuroregeneration and remyelination2. These different characteristics present the astrocyte as a versatile player in regulatory processes depending on context and time of injury and disease. 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 also share their lineage with oligodendrocytes and interact with these myelin forming cells by sharing gap junctions allowing passage of small metabolites and molecules for communication6. Oligodendrocytes have the highest metabolic rate of cells in the CNS, producing myelin up to three times their weight per day for up to 50 axons each. The myelin sheaths are critical for action potentials and need to be maintained constantly7. Additionally, oligodendrocytes provide axons with trophic support and are crucial for neuronal functionality2,7. Due to their high turnover of myelin oligodendrocytes are sensitive to reactive oxygen species and oxidative stress7,8. They have been shown to participate intricately in immune mediated processes by producing immune regulatory factors and expressing receptors to communicate with microglia9. As it becomes more apparent that astrocytes participate in immune mediated processes as well, their cross-talk with oligodendrocytes might elucidate new mechanisms in neuroinflammatory diseases. The importance of astrocytes in oligodendrocyte functioning is exemplified in primary astrocytopathies such as Alexander disease (AxD) and vanishing white matter (VWM)10 where astrocytedamage leads todemyelinationandoligodendrocytedeath. Inosmoticdemyelination syndrome astrocyte death is observed due to loss of gap junctions and proteostasis defects in astrocytes prior to oligodendrocyte loss and demyelination11-13. In addition, astrocyte dysfunction has been associated with many other neurological diseases including epilepsy14, amyotrophic lateral sclerosis (ALS)15, Huntington’s disease (HD)16, and Alzheimer’s disease (AD)17. In neuroinflammatory diseases, such as multiple sclerosis (MS) oligodendrocyte loss might be a consequence of aberrant immune responses. MS is characterized by inflammatory lesions with demyelination, neurodegeneration, and astrogliosis, in which astrocytes and oligodendrocytes are damaged18,19. Similarly, numerous other white matter disorders also show important cross-talk between astrocytes and oligodendrocytes (Table 1)10. Here we review the evidence for cross-talk between astrocytes and oligodendrocytes demonstrating an emerging role for astrocytes in oligodendrocyte damage, as well as contributing to tissue regeneration and remyelination. Understanding how astrocytes
RkJQdWJsaXNoZXIy MTk4NDMw