Diminished Schwann Cell Repair Responses Underlie Age-Associated Impaired Axonal Regeneration

We demonstrate that 24-month-old mice exhibit an impairment of functional recovery after nerve injury compared to 2-month-old animals

Michio W. Painter

2014

Scholarcy highlights

  • Successful regeneration of the peripheral nervous system requires the coordinated activity of several distinct yet interlocking systems
  • Our results demonstrate that extrinsic factors are sufficient to rejuvenate the age-associated decline in mammalian axonal regeneration, and broadly reveal how Schwann cells function and its response to axonal injury alters during normal aging, resulting in slower dedifferentiation and myelin clearance
  • Previous studies have established in rodents that fewer axons regenerate after injury in aged animals, it is unclear how this might translate into functional recovery, a more meaningful clinical parameter
  • 15 days after injury, while motor function is restored by day 30, reflecting the short distances and consistent with axon growth of 1–2 mm per day, similar to that found in humans
  • We found that neuronal intrinsic growth responses are unaltered with normal aging and that aged neurons can be fully ‘‘primed’’ to regenerate after an axonal injury supported by an undiminished injuryinduced transcriptional change
  • These observations indicate that deficient axonal regeneration in aged animals arises from a dominant extrinsic inhibition of neuronal outgrowth by the aged microenvironment, and suggest that functional recovery after axotomy may be enhanced throughout life via neuron-extrinsic mechanisms
  • These results suggest that the age-associated decline in axonal regeneration results from diminished Schwann cell plasticity, leading to slower myelin clearance

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