Author/Editor     Faroni, A.; Smith, R. J. P.; Procacci, P.; Castelnovo, L. F.; Puccianti, E.; Reid, A. J.; Magnaghi, V.; Verkhratsky, Alexei
Title     Purinergic signaling mediated by P2X7 receptors controls myelination in sciatic nerves
Type     članek
Vol. and No.     Letnik 92, št. 10
Publication year     2014
Volume     str. 1259-1269
ISSN     0360-4012 - Journal of neuroscience research
Language     eng
Abstract     Adenosine-5 0 -triphosphate, the physiological ligand of P2X receptors, is an important factor in peripheral nerve development. P2X 7 receptor is expressed in Schwann cells (SCs), but the specific effects of P2X 7 purinergic sig- naling on peripheral nerve development, myelination, and function are largely unknown. In this study, sciatic nerves from P2X 7 knockout mice were analyzed for altered expression of myelin-associated proteins and for altera- tions in nerve morphology. Immunohistochemical analy- ses revealed that, in the wild-type peripheral nerves, the P2X 7 receptor was localized mainly in myelinating SCs, with only a few immunopositive nonmyelinating SCs. Complete absence of P2X 7 receptorproteinwascon- firmed in the sciatic nerves of the knockout mice by Western blot and immunohistochemistry. Western blot analysis revealed that expression levels of the myelin pro- teins protein zero and myelin-associated glycoprotein are reduced in P2X 7 knockout nerves. In accordance with the molecular results, transmission electron microscopy anal- yses revealed that P2X 7 knockout nerves possess signifi- cantly more unmyelinated axons, contained in a higher number of Remak bundles. The myelinating/nonmyelinat- ing SC ratio was also decreased in knockout mice, and we found a significantly increased number of irregular fibers compared with control nerves. Nevertheless, the myelin thickness in the knockout was unaltered, suggest- ing a stronger role for P2X 7 in determining SC maturation than in myelin formation. In conclusion, we present mor- phological and molecular evidence of the importance of P2X 7 signaling in peripheral nerve maturation and in determining SC commitment to a myelinating pheno- type.
Keywords     sciatic nerves
transmission electron microscopy
peripheral nerve
ishiadični živci
transmisijska elektronska mikroskopija
periferni živci