REVERSAL OF AXONAL TRANSPORT IN REGENERATING NERVES¹

Abstract

Abstract— Orthograde and retrograde axonal transport were studied in rat sciatic nerves which had been crushed and either allowed to regenerate, or prevented from doing so by tightly ligaturing the nerve. At various intervals after crushing the nerve. L‐[3H]leucine was injected into the lumbosacral spinal cord. and the subsequent transport of labeled protein in motoneuron axons was quantitated by measuring the accumulation of labeled protein at collection crushes made proximal to the original nerve crush. Accumulations proximal to the collection crushes (orthograde transport) 9‐11 h after injection (p.i.). decreased within I day of nerve injury, but returned to normal values as regeneration proceeded. In non‐regenerating nerves accumulations remained depressed for at least 30 days. Accumulations distal to the collection crushes (retrograde transport) 9‐11 h pi. increased over the first 5 days following injury but returned to normal values as regeneration proceeded. In non‐regenerating nerves accumulations remained elevated. The time‐course of retrograde transport of newly‐synthesized protein also returned to normal during nerve regeneration. It is suggested that changes in retrograde transport during regeneration may inform the neuron cell body of the progress of regeneration and elicit appropriate metabolic responses. among which may be the changes in orthograde transport that follow axotomy.

Turnaround of Axoplasmic Transport of Selected Particle‐Specific Enzymes at an Injury in Control and Diisopropylphosphorofluoridate‐Treated Rats

“…It has been argued that turnaround in normal nerve may occur all along the axon (Bulger and Bisby, 1978). Kirkpatrick et al (1972) reported that particles visualized by Nomarski optics in the sciatic nerve of chicken sometimes reversed their course.…”

“…It may play a role in signalling to t h e perikaryon the fact of injury (Cragg, 1970;Grafstein, 1975). Perhaps turnaround, coupled with alterations in the amounts of materials exported from the perikaryon (Schmidt and McDougal, 1978; Bulger and Bisby, 1978), keeps the new terminal sufficiently clear of presumably unneeded organelles so that regeneration can proceed.…”

Axonal transport and MR imaging: Prospects for contrast agent development

“…Transported vesicles, proteins, and mitochondria pile up at the ligation site. A signal that goes back to the cell body then causes anterograde fast transport to halt (62,63). This situation continues until a critical concentration of cytoskeletal subunits accumulates through slow transport, permitting axonal growth to begin.…”

Decreased axonal transport of structural proteins in streptozotocin diabetic rats.

“…We have recently reported that the amount of retrogradely transported glycoproteins within the axons is decreased in streptozotocin diabetic rats (14,15). Materials carried by retrograde axonal transport possibly influence the protein synthesis in the cell body (23)(24)(25), and we have indeed demonstrated structural changes ofthe nerve cell bodies in this model (26). Therefore, we suggest that the impaired retrograde transport is the trigger for changes in synthesis of protein in the nerve cell body and in turn is responsible for the decreased slow axonal transport.…”