Effects of age-related loss of P/Q-type calcium channels in a mice model of peripheral nerve injury

Abstract

We analyzed the role of P/Q-type calcium channels in sciatic nerve regeneration after lesion induced by chronic constriction injury (CCI) in heterozygous null mutant mice lacking the CaV2.1α1 subunit of these channels (Cacna1a+/−). Compared with wild type, Cacna1a+/− mice showed an initial reduction of the CCI-induced allodynia, indicating a reduced pain perception, but they also evidenced a lack of recovery over time, with atrophy of the injured hindpaw still present 3 months after CCI when wild-type mice fully recovered. In parallel, Cacna1a+/− mice exhibited an early onset of age-dependent loss of P/Q-type channels, which can be responsible for the lack of functional recovery. Moreover, Cacna1a+/− mice showed an early age-dependent reduction of muscular strength, as well as of Schwann cells proliferation and sciatic nerve remyelination. This study demonstrates the important role played by P/Q-type channels in recovery from nerve injury and has important implications for the knowledge of age-related processes.