Journal
NEUROBIOLOGY OF AGING
Volume 36, Issue 1, Pages 352-364Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.neurobiolaging.2014.07.025
Keywords
Cacna1a; P/Q-type channels; Allodynia; Nerve regeneration; Schwann cells; Muscle
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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 Ca(V)2.1 alpha(1) 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. (C) 2015 Elsevier Inc. All rights reserved.
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