Non-cell autonomous mechanisms of proliferation and differentiation of oligodendrocyte precursor cells

抄録

The concept of the neurovascular unit is now relatively well accepted. The neurovascular unit emphasizes that cell-cell interaction between neuronal, glial, and vascular elements is critical for brain function. Within the neurovascular unit in cerebral white matter, oligodendrocyte precursor cells (OPCs) may receive/provide trophic support from/to neighboring cells to maintain proper white matter function. During development or after white matter damage, OPCs proliferate and migrate to their target regions, where they differentiate into oligodendrocytes and form myelin sheaths. For OPC proliferation and differentiation, trophic support from neighboring cells, such as astrocytes and pericytes, would be needed. For example, astrocytes produce brain-derived neurotrophic factor that promotes oligodendrogenesis (i.e. OPC proliferation and differentiation) to ease white matter damage under pathological conditions. In addition, pericytes also secrete several soluble factors, at least partly through the function of intracellular A-kinase anchor protein 12 (AKAP12). When AKAP12 is knocked down, AKAP12-deficient pericytes no longer support OPC proliferation and differentiation. On the contrary, OPCs may also secrete soluble factors to regulate the microenvironment within the neurovascular unit. Under physiological conditions, OPCs are an important source of transforming growth factor-β1 that supports blood-brain barrier integrity. But after white matter injury, OPCs can rapidly respond to the stress and produce matrix metalloproteinase-9 that leads to BBB leakage and triggers secondary cascades of cerebrovascular injury and demyelination. Because white matter damage is one of the major hallmarks of several cerebrovascular diseases and because OPCs are an important cell type for white matter function, understanding and dissecting these OPC-related non-cell autonomous mechanisms in the neurovascular unit may lead to novel opportunities for white matter protection and white matter recovery.