Blockade of retrograde axonal transport delays the onset of metabolic and morphologic changes induced by axotomy.

Axotomy-induced increase in 2-deoxyglucose (2-DG) uptake by motor nuclei and neuronal chromatolytic changes were studied after subepineural injection of colchicine into the motor nerve. Hypoglossal nuclei of either cats or rats were axotomized bilaterally, while one of the nerves was injected with colchicine or saline proximal to the site of nerve transection and the other was left intact or injected with saline. Colchicine abolished or decreased the uptake of 2-DG by axotomized nuclei and delayed the onset of chromatolysis. The decrease in 2-DG uptake was observed in rat hypoglossal nuclei between 24 and 48 hr but not 5 days after drug treatment. In turn, a delay in the onset of chromatolysis was observed in cat hypoglossal nuclei at 14 days but not 30 days after treatment. Saline did not prevent chromatolysis nor the increased uptake of 2-DG. Colchicine injected intraneurally in intact preparations did not result in chromatolysis or in increased 2-DG uptake. Following colchicine injection, the drug remained localized near the site of injection and blocked retrograde axonal transport of horseradish peroxidase in the hypoglossal nerve. These findings suggest that the onset of chromatolysis and of the increase in 2-DG uptake after axotomy are partly dependent upon retrograde axonal transport.