A2  Adenosine Receptors and Sphingosine 1-Phosphate Signaling Cross-Talk in Oligodendrogliogenesis.
Oligodendrocyte-formed myelin sheaths allow fast synaptic transmission in the brain. Impairments in the process of myelination, or demyelinating insults, might cause chronic diseases such as multiple sclerosis (MS). Under physiological conditions, remyelination is an ongoing process throughout adult life consisting in the differentiation of oligodendrocyte progenitor cells (OPCs) into mature oligodendrocytes (OLs). During pathological events, this process fails due to unfavorable environment. Adenosine and sphingosine kinase/sphingosine 1-phosphate signaling axes (SphK/S1P) play important roles in remyelination processes. Remarkably, fingolimod (FTY720), a sphingosine analog recently approved for MS treatment, plays important roles in OPC maturation. We recently demonstrated that the selective stimulation of A2  adenosine receptors (A2  Rs) inhibit OPC differentiation in vitro and reduce voltage-dependent outward K+ currents (I  ) necessary to OPC maturation, whereas specific SphK1 or SphK2 inhibition exerts the opposite effect. During OPC differentiation A2  R expression increases, this effect being prevented by SphK1/2 blockade. Furthermore, selective silencing of A2  R in OPC cultures prompts maturation and, intriguingly, enhances the expression of S1P lyase, the enzyme responsible for irreversible S1P catabolism. Finally, the existence of an interplay between SphK1/S1P pathway and A2  Rs in OPCs was confirmed since acute stimulation of A2  Rs activates SphK1 by increasing its phosphorylation. Here the role of A2  R and SphK/S1P signaling during oligodendrogenesis is reviewed in detail, with the purpose to shed new light on the interaction between A2  Rs and S1P signaling, as eventual innovative targets for the treatment of demyelinating disorders.
['Coppi|Elisabetta|E|', 'Cencetti|Francesca|F|', 'Cherchi|Federica|F|', 'Venturini|Martina|M|', 'Donati|Chiara|C|', 'Bruni|Paola|P|', 'Pedata|Felicita|F|', 'Pugliese|Anna Maria|AM|']
adenosine remyelination oligodendrocyte progenitor cells (OPCs) A2B receptors K+ channels oligodendrocyte differentiation sphingosine kinase (SphK) sphingosine-1-phosphate