Each year over one million Americans suffer from damage or injury to the central nervous system (i.e., head injury, stroke, and brain tumors). In addition, diseases related to aging such as presenile dementia and Alzheimer's Disease are a serious health problem. One of the major goals of basic and clinical research in the Neurosciences is to find new ways to improve recovery and quality of life. The proposed project provides a means of studying the unique process of neurogenesis and nerve cell replacement that takes place in the hamster olfactory system. Two procedures will be used to induce degeneration of sensory neurons: nerve transection and chemical exposure. Subsequent neurogenesis and recovery will be studied using quantitative methods to determine the capacity of replacement neurons to reestablish connections with the central nervous system and to restore function. Recovery after nerve transection will be investigated in: 1) Anatomical studies to determine if replacement neurons have the capacity to restore axon connections to specific target regions in the olfactory bulb, 2) Electrophysiological studies to determine the response of reconnected cells (receptive fields and odor response), and 3) Behavioral studies to determine if animals can detect and respond to sensory stimuli. Recovery from exposure of the nasal cavity to environmental agents (chemicals and metallic dusts) will also be investigated in the hamster. Data from animal experiments will be compared to human autopsy and surgical pathology findings to investigate cellular mechanisms underlying nasal disease. A finding that functional recovery occurs in the hamster olfactory system would suggest that, contrary to current dogma, replacement of neurons and repair of damaged pathways in the mammalian nervous system is possible. This proposal addresses important questions about the potential for neuron replacement and functional repair of damage within the central nervous system. The unique capacity of olfactory neurons for continued neurogenesis provides an excellent model in which to study this process. The results from the proposed experiments could provide a significant breakthrough for the field of neural regeneration and findings may have direct clinical application.
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