Motoneurons innervating partially denervated rat hindlimb muscles remain susceptible to axotomy-induced cell death

doi:10.1016/S0306-4522(98)00037-2

Neuroscience

Volume 86, Issue 1, 21 May 1998, Pages 291-299

https://doi.org/10.1016/S0306-4522(98)00037-2 Get rights and content

Abstract

Tibialis anterior and extensor digitorum longus muscles were partially denervated by cutting the L4 spinal nerve in three-day-old rats. The ultrastructure of the intact axons to these muscles in the L5 spinal nerve was examined in nine-day-old rats. In the control L5 spinal nerve, myelinated and unmyelinated axons were intermingled throughout the cross-section of the nerve, while on the operated side the nerve contained areas with predominantly small unmyelinated immature axons. The number of motoneurons innervating the partially denervated muscles was established by retrograde labelling with Diamidino Yellow. In nine- and 21-day-old rats, the number of labelled motoneurons on the partially denervated side, expressed as a percentage of the control side, was 26.1±5.5% and 20.7±3.0%, respectively. The response of these uninjured motoneurons to axotomy was tested. The axons of the motoneurons to the partially denervated muscles were crushed at nine days and the numbers of labelled motoneurons in the spinal cord of these rats counted at 21 days of age. Only 4.9±2.0% labelled motoneurons were seen on the operated side, as opposed to 20.7±3.0% present in animals without sciatic nerve injury. In normal animals, nerve injury at nine days does not cause motoneuron death.

Thus, motoneurons to partially denervated muscles (i) have axons with several immature features and (ii) remain susceptible to axotomy-induced death for much longer than normal.

Section snippets

Experimental procedures

Four different experimental procedures were carried out on Sprague–Dawley rats (Biological Services, UCL), and these are summarized in Table 1.

Ultrastructure of the L5 spinal nerve after removal of the L4 spinal nerve

In rats of Group 1, the L4 SN was sectioned on one side at three days, and six days later the uninjured L5 SN that contained the undamaged axons to the partially denervated EDL and TA muscles, and the contralateral control L5 SN, were removed and processed for ultrastructural analysis (see Table 1).

Fig. 1 shows typical examples of semi-thin sections (0.5 μm) of the L5 SN taken from both sides of a nine-day-old rat in which the L4 SN was removed from one side at three days of age. Fig. 1A shows

Discussion

In the present study, changes of intact motor axons and motoneurons to muscles that had lost most of their innervation were examined. The reduction of innervation was achieved by partial denervation of EDL and TA muscles at three days of age. The results of this study show that removal of the main source of innervation to these muscles at three days of age (i) prevents the maturation of the remaining intact motor axons and (ii) maintains the susceptibility of their motoneurons to

Conclusion

We propose that many of the remaining uninjured axon terminals in these partially denervated muscles, whose axons originate from the L5 SN, will either revert to, or remain, growing structures in order to innervate the otherwise denervated muscle fibres. It is likely that this will delay the transition of their motoneurons from growing into transmitting cells. This prolonged period of axonal growth may account for the fact that these motoneurons remain susceptible to death following nerve

Acknowledgements

We are grateful to Action Research, The Wellcome Trust and The Muscular Dystrophy Group of Great Britain. We would also like to thank Mark Turmaine and Jim Dick for their invaluable technical help.

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Motoneurons innervating partially denervated rat hindlimb muscles remain susceptible to axotomy-induced cell death

Abstract

Section snippets

Experimental procedures

Ultrastructure of the L5 spinal nerve after removal of the L4 spinal nerve

Discussion

Conclusion

Acknowledgements

J. Neurosci. Meth.

Neuroscience

Devl Brain Res.

Neuroscience

Devl Brain Res.

Neuroscience

Devl Brain Res.

Trends Neurosci.

Fedn Eur. biochem. Socs Lett.

Neuroscience

The effects of partial denervation at birth on the development of muscle fibres and motor units in rat lumbrical muscle

J. Physiol.

GAP-43 mRNA in mouse motoneurons undergoing axonal sprouting in response to muscle paralysis or partial denervation

Eur. J. Neurosci.

Nodal and terminal sprouting from motor nerves from fast and slow muscles of the mouse

J. Physiol.

Motoneurone sprouting induced by prolonged tetrodotoxin block of nerve action potentials

Nature

Polyneuronal innervation of skeletal muscle in new-born rats and its elimination during maturation

J. Physiol.