Abstract
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 A1 receptors, promotes oligodendrocyte maturation and inhibits their proliferation; on the contrary, by stimulating A2A receptors, it inhibits oligodendrocyte maturation. A1 and A2A receptor-mediated effects are related to opposite modifications of outward delayed rectifying membrane K+ currents (IK) that are involved in the regulation of oligodendrocyte differentiation. Brain A1 and A2A receptors might represent new molecular targets for drugs useful in demyelinating pathologies, such as multiple sclerosis (MS), stroke and brain trauma.
Highlights
Elisabetta Coppi 1, Lucrezia Cellai 2, Giovanna Maraula 2, Ilaria Dettori 2, Alessia Melani 2, Anna Maria Pugliese 2 and Felicita Pedata 2*
We have demonstrated that the activation of GPR17, a recently deorphanized Gi-coupled P2Ylike receptor, which stimulates oligodendrocyte progenitor cells (OPCs) differentiation (Lecca et al, 2008; Fumagalli et al, 2011), elicits opposite effects in comparison to the Gs coupled A2A subtype, increasing the amplitude of IK currents recorded from cultured OPCs (Coppi et al, 2013a)
A1 receptors are causative of hypoxia-induced brain injury and ventriculomegaly during early postnatal development (Turner et al, 2002, 2003), antagonism of adenosine A1 receptors is relevant in the action mechanism of caffeine
Summary
Elisabetta Coppi 1, Lucrezia Cellai 2, Giovanna Maraula 2, Ilaria Dettori 2, Alessia Melani 2, Anna Maria Pugliese 2 and Felicita Pedata 2*. Reviewed by: Micaela Morelli, University of Cagliari, Italy Hariharasubramanian Ramakrishnan, State University of New York, USA. F (2015) 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. A1 and A2A receptor-mediated effects are related to opposite modifications of outward delayed rectifying membrane K+ currents (IK) that are involved in the regulation of oligodendrocyte differentiation.
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