Degeneration of a muscle following remote nerve damage: Physiological changes and triggering mechanisms
AdvisorChapman, Reginald F.
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PublisherThe University of Arizona.
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AbstractMuscle depends on innervation and contraction to maintain a differentiated state. Denervation or disuse, therefore, often leads to muscle atrophy. In grasshoppers, muscle degeneration can also be induced when a hindlimb is lost by autotomy. In this case, the thoracic muscles which degenerate are neither damaged nor denervated, suggesting the existence of transneuronal mechanisms that influence muscle survival. Arbas and Weidner (1991) found that muscle degeneration is induced when the leg nerve (which does not innervate the thoracic muscles) is severed during autotomy. To characterize this autotomy-induced degenerative process, I studied a thoracic tergotrochanteral depressor muscle (M#133b,c) subsequent to autotomy in the grasshoppers, Barytettix psolus and B. humphreysii. The degeneration of M#133b,c is generally complete by 15 days after autotomy, when muscle cross-sectional area is reduced to 4% of the contralateral-control. The rate of muscle degeneration is initially slow, but at ∼10 days post-autotomy, degeneration becomes rapid and muscle fiber number becomes reduced. During this rapid phase, degeneration of M#133b,c occurs by programmed cell death. Indicators of programmed cell death-up-regulation of ubiquitin--immunoreactivity, condensed nuclear chromatin and DNA fragmentation--are all present 10 and 15 days post-autotomy. The rapid phase of M#133b,c degeneration is also characterized by 'denervation-like' changes in fiber electrophysiology including depolarized resting membrane potentials, post-inhibitory rebound, smaller evoked excitatory junctional potentials and an increased frequency of spontaneous miniature potentials. The initial trigger for autotomy-induced muscle degeneration appears to be the loss of some proprioceptive input, since severing of afferents from the subgenual organ leads to muscle degeneration. The loss of exteroceptive chemo or mechanoreceptor input, however, does not lead to degeneration. Autotomy is also correlated with a decline in activity in the nerve innervating M#133b,c during the period of programmed cell death. The population of active motor units within the nerve is also decreased during this period. These findings suggest the transneuronal mechanisms that influence muscle degeneration following autotomy. The loss of proprioceptive input probably leads to deafferentation of motoneurons within the metathoracic ganglion. The deafferentated motoneurons have a decreased level of spontaneous activity which triggers the subsequent muscle degeneration by programmed cell death.
Degree ProgramGraduate College