Acta Neuropathologica

, Volume 84, Issue 1, pp 89–93 | Cite as

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

  • Roger Pamphlett
  • Alexandra Bayliss
Regular Papers


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.

Key words

Lead Motor axons Neuromuscular junction Nerve crush Botulinum toxin 


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  1. 1.
    Baruah JK, Rasool CG, Bradley WG, Munsat TL (1981) Retrograde axonal transport of lead in rat sciatic nerve. Neurology 31:612–616Google Scholar
  2. 2.
    Conradi S, Ronnevi LO, Vesterberg O (1976) Abnormal tissue distribution of lead in amyotrophic lateral sclerosis. J Neurol Sci 29:259–265Google Scholar
  3. 3.
    Cooper GP, Manalis RS (1984) Cadmium: effects on transmitter release at the frog neuromuscular junction. Eur J Pharmacol 99:251–256Google Scholar
  4. 4.
    Duchen LW (1971) An electron microscopic study of the changes induced by botulinum boxin in the motor end-plates of slow and fast skeletal muscle fibres of the mouse. J Neurol Sci 14:47–60Google Scholar
  5. 5.
    Kristensson K, Olsson Y, Sjöstrand J (1971) Axonal uptake and retrograde transport of exogenous proteins in the hypoglossal nerve. Brain Res 32:399–406Google Scholar
  6. 6.
    Mahaffey KR, Rader JI (1980) Metabolic interactions: lead, calcium, and iron. Ann NY Acad Sci 355:285–297Google Scholar
  7. 7.
    Manalis RS, Cooper GP, Pomeroy SL (1984) Effects of lead on neuromuscular transmission in frog. Brain Res 294:95–109Google Scholar
  8. 8.
    Miledi R, Slater CR (1970) On the degeneration of the rat neuromuscular junctions after nerve section. J Physiol (London) 207:507–528Google Scholar
  9. 9.
    Mitchell JD (1987) Heavy metals and trace elements in amyotrophic lateral sclerosis. Neurol Clin 5:43–60Google Scholar
  10. 10.
    Nakamura T, Namba T, Grob D (1967) Motor end plate reactivity to divalent metal ions: histochemical studies. J Histochem Cytochem 15:276–284Google Scholar
  11. 11.
    Nakamura T, Torigoe K, Takahashi A (1983) On the connection between the sarcoplasmic reticulum and the junctional folds in mouse neuromuscular junction. Okajimas Folia Anat Jpn 60:161–174Google Scholar
  12. 12.
    Pamphlett R, Bayliss A (1992) Lead uptake in motor axons. Muscle Nerve (in press)Google Scholar
  13. 13.
    Pumplin DW, Reese TS (1977) Action of brown widow spider venom and botulinum toxin on the frog neuromuscular junction examined with the freeze-fracture technique. J Physiol (London) 273:443–457Google Scholar
  14. 14.
    Silbergeld EK, Adler HS (1978) Subcellular mechanism of lead neurotoxicity. Brain Res 148:451–467Google Scholar

Copyright information

© Springer-Verlag 1992

Authors and Affiliations

  • Roger Pamphlett
    • 1
  • Alexandra Bayliss
    • 1
  1. 1.Department of PathologyUniversity of SydneySydneyAustralia

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