Role of adenosine in oligodendrocyte precursor maturation

Differentiation and maturation of oligodendroglial cells are postnatal processes that involve specific morphological changes correlated with the expression of stage-specific surface antigens and functional voltage-gated ion channels. A small fraction of oligodendrocyte progenitor cells (OPCs) generated during development are maintained in an immature and slowly proliferative or quiescent state in the adult central nervous system (CNS) representing an endogenous reservoir of immature cells. Adenosine receptors are expressed by OPCs and a key role of adenosine in oligodendrocyte maturation has been recently recognized. As evaluated on OPC cultures, adenosine, by stimulating A(1) receptors, promotes oligodendrocyte maturation and inhibits their proliferation; on the contrary, by stimulating A(2A) receptors, it inhibits oligodendrocyte maturation. A(1) and A(2A) receptor mediated effects are related to opposite modifications of outward delayed rectifying membrane K+ currents (I-K) that are involved in the regulation of oligodendrocyte differentiation. Brain A(1) and A(2A) receptors might represent new molecular targets for drugs useful in demyelinating pathologies, such as multiple sclerosis (MS), stroke and brain trauma.