Alpha Omega Alpha Honor Medical Society

2014 Research Abstract

The role of mTOR in exercise dependent axon regeneration through a peripheral nerve graft following spinal cord injury

Investigator: Matthew Recker, Drexel University College of Medicine

Mentor: John D. Houle, PhD

Abstract:
Mammalian target of rapamycin (mTOR) – a signaling molecule involved in protein synthesis, cell growth, and cell proliferation – has been shown to be involved in neural plasticity and regeneration in the CNS. Forced exercise following spinal cord injury in rats causes an upregulation of neurotrophic factors and an increase in axon regeneration through a peripheral nerve graft (PNG). The aim of this study is twofold: to determine whether mTOR signaling is a necessary component of axonal regeneration through a PNG following spinal cord transection and to determine whether mTOR signaling is responsible for the increase in regeneration with forced exercise. This is accomplished using rapamycin, which blocks mTOR signaling. Axons damaged during spinal cord transection will regenerate through a PNG that has been apposed to the lesion. Neurons whose axons regenerated through the graft can then be labeled by applying the retrograde fluorescent tracer True Blue to the distal end of the graft. Therefore, the number of True Blue positive neurons in the spinal cord serves to quantify regenerative capacity.

In all rats, a complete spinal cord transection was performed at T12 and a graft from the tibial nerve of a donor rat was apposed to the spinal cord. The number of regenerating neurons was compared between four cohorts:

  • T12 transection (Tx), PNG, no exercise, no rapamycin (Tx+PNG)
  • T12 transection, PNG, no exercise, rapamycin (Rap) (Tx+PNG+Rap)
  • T12 transection, PNG, exercise (Ex), no rapamycin (Tx+PNG+Ex)
  • T12 transection, PNG, exercise, rapamycin (Tx+PNG+Ex+Rap)
Florescence microscopy was utilized to identify and manually count True Blue positive neurons in the spinal cord. Data collection for this project is currently incomplete. Thus far, the data shows a significant decrease in the number of regenerating neurons in rapamycin treated animals rostral to the lesion cavity. These data suggest, as demonstrated by other researchers, that mTOR signaling is an integral component of the regenerative response of injured CNS neurons. Completion of the project will allow for evaluation of the role of mTOR in the exercise-induced increase in regenerative potential.

Last modified: 9/11/2015

Updated on September 11, 2015.


© 2017 Alpha Omega Alpha Honor Medical Society