Adenosine Helps Wrap Things Up in the CNS

Science's STKE  10 Dec 2002:
Vol. 2002, Issue 162, pp. tw463-TW463
DOI: 10.1126/stke.2002.162.tw463

The rapid conduction of nerve impulses in vertebrates depends on insulation of the axons by myelin, which is synthesized by oligodendrocytes in the central nervous system (CNS) and Schwann cells in the peripheral nervous system (PNS). In the PNS, neuronal activity inhibits myelination, a process that involves neuronal release of adenosine triphosphate (ATP) and activation of ATP-selective purinergic P2Y receptors on Schwann cells. In the CNS, however, neuronal activity promotes myelination. Stevens et al. used cultured mouse dorsal root ganglion (DRG) cells and rat or mouse oligodendrocyte progenitor cells (OPCs) to investigate the relationship between neuronal activity and oligodendrocyte development and myelination. The authors used pharmacological analysis together with reverse transcriptase polymerase chain reaction and calcium (Ca2+) imaging to demonstrate functional adenosine-selective purinergic receptors in cultured rat OPCs and freshly isolated mouse OPCs. Time-lapse Ca2+ imaging revealed that OPCs cocultured with DRG neurons responded to DRG firing with increased intracellular Ca2+, a response that was blocked by purinergic antagonists. Both DRG activity and adenosine inhibited OPC proliferation; the inhibitory effect of DRG firing was blocked by adenosine antagonists. Adenosine stimulated OPC differentiation, evaluated by the appearance of cell stage-dependent markers; altered OPC morphology; and promoted myelination of DRG axons by OPCs. Electrical stimulation of DRGs also promoted myelination, which was sensitive to adenosine receptor anatgonists. These data indicate that adenosine released during neuronal activity can promote myelination in the developing CNS; the difference in the response to neuronal activity by Schwann cells in the PNS and oligodendrocytes in the CNS may depend, at least in part, on the presence or absence of functional adenosine-selective purinergic receptors.

B. Stevens, S. Porta, L. L. Haak, V. Gallo, R. D. Fields, Adenosine: a neuron-glial transmitter promoting myelination in the CNS in response to action potentials. Neuron 36, 855-868 (2002). [Online Journal]