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Degenerative and regenerative changes after loss of neuromuscular interaction during early postnatal life

Harding, Duncan Ian; (1997) Degenerative and regenerative changes after loss of neuromuscular interaction during early postnatal life. Doctoral thesis (Ph.D), UCL (University College London). Green open access

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Abstract

Young motoneurones are critically dependent upon functional interaction with their target muscle for their normal development, and if deprived of target contact a large proportion die. This thesis is concerned with changes induced by loss of nerve-muscle interaction during early postnatal life, and examines the possibility that motoneurones which are not allowed to mature during this critical period are more vulnerable. It was found that stabilising neuromuscular contacts on reinnervation after nerve crush at birth or prolonged neonatal muscle paralysis, by inhibiting the calcium- activated neutral protease with leupeptin, rescued motoneurones that would otherwise die. In the case of nerve crush this lead to a significant improvement in muscle recovery. The time-course of motoneurone death following a prolonged period of neonatal muscle paralysis was studied, and motoneurones were observed to die by 3 weeks of age. The structural changes in the nerve to soleus following neonatal nerve injury or muscle paralysis were examined, and it was found that although motor and sensory myelinated axons were lost in the nerve after nerve injury, only motor myelinated axons were lost after muscle paralysis. Finally, the thesis explored the possibility that motoneurones supplying a partially denervated muscle may remain in a growing mode for longer, and could be susceptible to nerve crush injury at a time when they would normally survive this insult. It was found that the remaining motoneurones supplying the EDL and TA muscles, after these muscles had been partially denervated at 3 days of age, died when the sciatic nerve was crushed at 9 days of age. The results of this study illustrate the importance of nerve-muscle interaction in the developing neuromuscular system, and show that this is a time when even a slight perturbation can have permanent effects.

Type: Thesis (Doctoral)
Qualification: Ph.D
Title: Degenerative and regenerative changes after loss of neuromuscular interaction during early postnatal life
Open access status: An open access version is available from UCL Discovery
Language: English
Additional information: Thesis digitised by ProQuest.
Keywords: Biological sciences; Motor neurons
URI: https://discovery.ucl.ac.uk/id/eprint/10103673
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