AGING AND NEUROMUSCULAR DEGENERATION AND REGENERATION

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The responses of motor neurons and muscles to axon injury have been well characterized in newborn through young adult animals, but they have not been examined in aged animals. In view of the anabolic nature of the axon reaction, increasing evidence that advancing age alters neuronal energy metabolism, and the independent effects of advancing age on muscle fibers, it is the aim of this research to determine whether the patterns of degenerative and regenerative changes in neurons and target muscles are the same after axon injury in young adult and middle-aged animals. This question is important for better understanding of age-related differences in the process of peripheral nerve regeneration and muscle reinnervation in the aging human population following axon trauma. Furthermore, it shall provide spacial, temporal, and metabolic frames of reference for subsequent studies conducted on any one part of the neuromuscular system, at any age. The proposed study examines several regions of a specific neuromuscular system and compares the nature and significance of axotomy-induced morphological and enzymatic changes in young adult (3-month old) and middle-aged (15-month old) rats. The model to be used is the motor neuron of the facial nucleus, and two forms of axon injury of differing severity are proposed. Thus at the site where the facial nerve exits the skull at the stylomastoid foramen, this nerve will be either crushed and reinnervation allowed to occur, or ligated and a segment excised to prevent reinnervation. After a series of postoperative survival times, which range between 2 days and 4 months after injury, observations will be made on the following regions of the motor system: the neuronal cell bodies and their supporting neuroglial cells in the facial nucleus, the axons proximal to the injury in the facial nerve as it exits the brain stem, the distal axons in the buccal branch of the nerve beyond the site of the injury, the motor end plates terminating on the nasolabialis muscles, and the deafferented muscle fibers of the nasolabialis muscle. From observations, as well as computer-assisted stereological analysis of light, electron microscope and enzyme histochemical preparations of these regions at each of the postoperative times, it will be possible to identify differences in both the intensity and the temporal patterns of the response of the entire system to axon injury as influenced by both the age of the animal and the severity of the axon injury.