Anales RANF

S13-03 PURINERGIC SIGNALLING IN THE OLIGODENDROGLIAL LINEAGE Arthur M. Butt University of Portsmouth, Portsmouth, U.K. Oligodendrocytes are the myelin-forming cells of the CNS and are derived from oligodendrocyte progenitor cells (OPCs). Myelinated axons are bundle together to form the white matter (WM) tracts of the CNS, providing for rapid communication throughout the CNS and integration. The main cells in myelinated tracts are oligodendrocytes and astrocytes, together with small populations of OPCs and microglia. The function of OPCs is to regenerate oligodendrocytes throughout life, to replace myelin lost through wear and tear and in pathology. A surprising aspect of WM physiology is the diversity of neurotransmitter signalling, with a key role for purinergic signalling. In physiology, astrocytes release ATP to activate purine receptors on OPCs and oligodendrocytes. In pathology, the release of ATP from damaged cells plays a role in both damage and repair by its direct effects on oligodenroglial integrity and survival, with prominent roles in ischemia, neuroinflammation, Multiple Scelerosis, and traumatic injury. The actions of ATP on oligodendroglia are mediated via a wide range of ionotropic P2X and P2Y G-protein coupled receptors (GPCR). In oligodendrocytes, predominant roles have been identified for P2X 7 and P2Y 1 receptor subtypes, which have a bipartite function, respectively mediating oligodendrocyte destruction and protection. In addition, glial ATP signalling may be altered with ageing and is implicated in impaired OPC regenerative capacity, which may be accelerated in Alzheimer’s disease. In summary, oligodendroglial purine receptors have a ‘Jeckyll and Hyde’ nature in oligodendroglial cells and a comprehensive understanding of the roles of the different purine receptors is critical if they are to provide potential therapeutic targets in multiple neuropathologies. Supported by a grant from the MRC