Axonal transport in the motor neurons of rats with neuropathy induced by p-bromophenylacetylurea.
Axonal transport was studied in sciatic motor neurons of rats with neuropathy induced by p-bromophenylacetylurea (BPAU) in dimethylsulfoxide solution. Control rats were treated with the vehicle alone. To label rapidly transported proteins, the rats received an injection of 35S-methionine into the ventral horn of the spinal cord at the L1 vertebral level. Radiolabeled protein was collected at ligatures applied on the sciatic nerve at intervals thereafter. In animals with severe motor weakness owing to treatment with BPAU, 400 mg/kg, there was evidence of increased delivery of labeled protein into the axon during the early period after isotope injection, but reduced delivery later. A dose-dependent decrease in the amount of labeled protein recirculated by retrograde axonal transport was also noted. A significant reduction in the amount of protein transported retrogradely was also detected during the latent subclinical phase of the neuropathy. The velocity of rapid anterograde transport, examined in unligated sciatic nerves, was unaffected by BPAU treatment. However, the lag time between precursor injection and the onset of transport was shorter in BPAU-treated rats than in controls. This effect was not explainable on the basis of fluctuations in core body temperature. The results are consistent with the view that disturbances of rapid anterograde and retrograde transport play a role in the peripheral neurotoxicity of BPAU. Attention is directed to the possibility that the transport disturbances and the subsequent neuropathy are related to alterations in the processing of rapidly transported membrane-limited organelles in the nerve cell bodies.
D000818:Animals; D001370:Axonal Transport; D008297:Male; D009046:Motor Neurons / Q000502:physiology*; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D010523:Peripheral Nervous System Diseases / Q000139:chemically induced / Q000503:physiopathology*; D051381:Rats; D014508:Urea / Q000031:analogs & derivatives* / Q000494:pharmacology
D009419:Nerve Tissue Proteins; C004506:4-bromophenylacetylurea; D014508:Urea