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

Neurobiol Aging. 2015 Jan;36(1):352-64. doi: 10.1016/j.neurobiolaging.2014.07.025. Epub 2014 Jul 25.

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.

Keywords: Allodynia; Cacna1a; Muscle; Nerve regeneration; P/Q-type channels; Schwann cells.

MeSH terms

  • Aging / metabolism*
  • Animals
  • Calcium Channels, P-Type / deficiency*
  • Calcium Channels, P-Type / metabolism*
  • Calcium Channels, P-Type / physiology
  • Calcium Channels, Q-Type / deficiency*
  • Calcium Channels, Q-Type / physiology
  • Disease Models, Animal
  • Mice, Inbred Strains
  • Nerve Regeneration / physiology
  • Peripheral Nerve Injuries / metabolism*
  • Peripheral Nerve Injuries / physiopathology
  • Sciatic Nerve / metabolism
  • Sciatic Nerve / physiology

Substances

  • Calcium Channels, P-Type
  • Calcium Channels, Q-Type