Premium
Purinergic signaling mediated by P2X 7 receptors controls myelination in sciatic nerves
Author(s) -
Faroni A.,
Smith R.J.P.,
Procacci P.,
Castelnovo L.F.,
Puccianti E.,
Reid A.J.,
Magnaghi V.,
Verkhratsky A.
Publication year - 2014
Publication title -
journal of neuroscience research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.72
H-Index - 160
eISSN - 1097-4547
pISSN - 0360-4012
DOI - 10.1002/jnr.23417
Subject(s) - purinergic receptor , knockout mouse , myelin , western blot , receptor , sciatic nerve , biology , purinergic signalling , microbiology and biotechnology , immunohistochemistry , medicine , endocrinology , neuroscience , anatomy , immunology , central nervous system , biochemistry , adenosine receptor , gene , agonist
Adenosine‐5′‐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 signaling 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 alterations in nerve morphology. Immunohistochemical analyses 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 receptor protein was confirmed in the sciatic nerves of the knockout mice by Western blot and immunohistochemistry. Western blot analysis revealed that expression levels of the myelin proteins protein zero and myelin‐associated glycoprotein are reduced in P2X 7 knockout nerves. In accordance with the molecular results, transmission electron microscopy analyses revealed that P2X 7 knockout nerves possess significantly more unmyelinated axons, contained in a higher number of Remak bundles. The myelinating/nonmyelinating 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, suggesting a stronger role for P2X 7 in determining SC maturation than in myelin formation. In conclusion, we present morphological and molecular evidence of the importance of P2X 7 signaling in peripheral nerve maturation and in determining SC commitment to a myelinating phenotype. © 2014 Wiley Periodicals, Inc.