The effect of nerve crush and botulinum toxin on lead uptake in motor axons

Abstract

After lead (Pb) is injected into striated muscle it binds to the sarcolemma of the neuromuscular junction (NMJ) and crosses into the terminal axons of motor neurons. To find out whether this intra-axonal accumulation of Pb is due to active transport or to diffusion down a concentration gradient, Pb uptake into motor axons of mice was studied at active and inactive NMJs. Twenty-four hours after sciatic nerve crush, 0.1 ml of 5% lead nitrate was injected into the tibialis anterior muscle and 30 min later the location of Pb was sought with electron microscopy and X-ray elemental analysis. A greatly reduced amount of Pb entered the axons after nerve crush compared to non-nerve crush animals, indicating that an active NMJ is required for intra-axonal Pb accumulation. To test if Pb could be entering the axon via recycling vesicles, botulinum toxin (BoTx) was injected into the muscle 24 h before Pb injection. There was no difference in intra-axonal Pb uptake in control and BoTx-injected animals, indicating that Pb is unlikely to use recycled vesicles to enter the axon.

Uptake of inorganic mercury by human locus ceruleus and corticomotor neurons: implications for amyotrophic lateral sclerosis

“…Uptake of toxic metals into LMNs has been well studied in rodents [41]. The pathway appears to be from circulating blood into striated muscle, from where the metals are taken up at the neuromuscular junction, either via calcium channels in the case of lead [59] or by recycling vesicles [60]. From the axon terminal the metals are retrogradely transported to the LMN cell body [41].…”