Effects mediated by alpha7 nicotinic receptor in rat Schwann cells: implications in peripheral nerve regeneration

Peripheral nerve fibers are able to regenerate. During nerve regeneration, Schwann cells (SCs) assume a phenotype known as Repair Schwann Cells, relevant for promoting an anti-inflammatory environment and axonal regeneration. SCs are cholinoceptive; in fact they express functional muscarinic cholinergic receptors favouring SCs differentiation towards myelinating phenotype (Loreti et al, 2007; Uggenti et al, 2014). Recently we have also characterized the expression of alpha7 nicotinic receptor. This receptor is fainlty expressed in sciatic nerve fibers and in SCs in vitro. Its expression significantly increases both in vivo and in vitro, after nerve injury or in presence of Bradykinin (Bk), a neuropeptide known for its pro-inflammatory effects. In fact we observed that sciatic nerve dissected and maintained in vitro for 24 hrs boh in absence or in presence of BK, showed a significant increase of alpha7 receptors. Moreover the selective activation of this receptor with (R)-ICH3 caused a modulation of uPA and MMPs responsible of the microenviroment modifications favouring Wallerian degeneration and promoting nerve regeneration. Similarly, the treatment of cultured SCs with BK appears to promote the repair Schwann cells phenotype, favouring the changing in cell morphology and up-regulating the expression of GFAP and c-jun. The activation of alpha7 receptor by selective agonist (R)-ICH3 after BK treatment, appears further promote this phenotype modulating inflammatory environment in terms of cytokines, growth factors and proteases production. These results suggest that alpha7 nicotinic receptor may be a cholinergic receptor expressed only by repair Schwann cells. Considering its anti-inflammatory role, alpha7 receptors may contribute to generate a microenviroment improving peripheral nerve regeneration. Loreti S., et al (2007) Neuron Glia Biology 3 : 269-279 Carolina Uggenti et al (2014). Dev. Neurobiol. 74:676-691 Piovesana R., et al (2018). J Cell Physiol. 233(7):5348-5360